Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

DNA origami involves the folding of long single-stranded DNA into designed structures with the aid of short staple strands; such structures may enable the development of useful nanomechanical DNA devices. Here we develop versatile sensing systems for a variety of chemical and biological targets at molecular resolution. We have designed functional nanomechanical DNA origami devices that can be used as 'single-molecule beacons', and function as pinching devices. Using 'DNA origami pliers' and 'DNA origami forceps', which consist of two levers similar to 170 nm long connected at a fulcrum, various single-molecule inorganic and organic targets ranging from metal ions to proteins can be visually detected using atomic force microscopy by a shape transition of the origami devices. Any detection mechanism suitable for the target of interest, pinching, zipping or unzipping, can be chosen and used orthogonally with differently shaped origami devices in the same mixture using a single platform.

DOI： 10.1038/ncomms1452

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

New types of noncovalent ribozyme-mimics for site-selective RNA scission are prepared by combining metal ions with oligonucleotides bearing an acridine. Lanthanide(III) ions and various divalent metal ions (Zn(II), Mn(II), Cu(II), Ni(II), Co(II), Mg(II), and Ca(II)) are employed without being bound to any sequence-recognizing moiety. The modified oligonucleotide forms a heteroduplex with the substrate RNA, and selectively activates the phosphodiester linkages in front of the acridine. As a result, these linkages are preferentially hydrolyzed over the others, even though the metal ions are not fixed anywhere. The scission is efficient under physiological conditions, irrespective of the sequence at the target site. Site-selective RNA scission is also successful with the combination of an oligonucleotide bearing an acridine at its terminus, another unmodified oligonucleotide, and the metal ion. In a proposed mechanism, the acridine pushes the unpaired ribonucleotide out of the heteroduplex and changes the conformation of RNA at the target site for the sequence-selective activation.

DOI： 10.1021/ja025653p

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Publishing type：Research paper (scientific journal)  

DOI： 10.1002/adtp.202300296

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DOI： 10.3390/gels10020139

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

Abstract

Topological gels possess structures that are cross‐linked only via physical constraints; ideally, no attractive intermolecular interactions act between their components, which yields interesting physical properties. However, most reported previous topological gels were synthesized based on supramolecular interlocked structures such as polyrotaxane, for which attractive intermolecular interactions are essential. Here, we synthesize a water‐soluble “molecular net” (MN) with a large molecular weight and three‐dimensional network structure using poly(ethylene glycol). When a water‐soluble monomer (N‐isopropylacrylamide) is polymerized in the presence of the MNs, the extending polymer chains penetrates the MNs to form an ideal topological MN gel with no specific attractive interactions between its components. The MN gels show unique physical properties as well a significantly high degree of swelling and high extensibility due to slipping of the physical cross‐linking. We postulate this method to yield a new paradigm in gel science with unprecedented physical properties.

DOI： 10.1002/anie.202317045

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.ijpharm.2024.123801

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society (ACS)  

DOI： 10.1021/acsbiomaterials.3c00327

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DOI： 10.1039/D2PY01574A

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Publishing type：Research paper (scientific journal)   Publisher：Springer Science and Business Media LLC  

Abstract

Adipose-derived stem cells (AdSCs), a type of mesenchymal stem cell, are expected to be applicable to regenerative medicine and cellular delivery systems. The maintenance of cell multipotency and control of the differentiation direction are important for these applications. However, the differentiation direction of these cells is widely believed to depend on the physical properties of their scaffold. In this study, we explored whether the multipotency of AdSCs, that is, their ability to differentiate into multiple cells, is maintained when they are removed from injectable polymer (IP) hydrogels with various degrees of cross-linking and induced to differentiate into osteoblasts and adipocytes. We confirmed that AdSCs cultured in IP hydrogels maintained an undifferentiated state. However, their differentiation into osteoblasts and adipocytes cannot be ensured; specifically, the multipotency of AdSCs may decrease when they are cultured in IP hydrogels. When cultured in an IP hydrogel with extreme softness and poor cell adhesion properties, the AdSCs remained in an undifferentiated state, but their multipotency was reduced. These results provide important insights into stem cell delivery systems using IP hydrogels.

DOI： 10.1038/s41428-022-00739-4

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Other Link： https://www.nature.com/articles/s41428-022-00739-4

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Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

Biodegradable double network (DN) gels with remarkably high mechanical strength and toughness were synthesised. The biodegradable DN gels can be potentially applied in biomedical applications such as cartilage regeneration.

DOI： 10.1039/d2py00360k

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Publishing type：Research paper (scientific journal)   Publisher：American Association for the Advancement of Science (AAAS)  

Cooperation is a strategy that has been adopted by groups of organisms to execute complex tasks more efficiently than single entities. Cooperation increases the robustness and flexibility of the working groups and permits sharing of the workload among individuals. However, the utilization of this strategy in artificial systems at the molecular level, which could enable substantial advances in microrobotics and nanotechnology, remains highly challenging. Here, we demonstrate molecular transportation through the cooperative action of a large number of artificial molecular machines, photoresponsive DNA-conjugated microtubules driven by kinesin motor proteins. Mechanical communication via conjugated photoresponsive DNA enables these microtubules to organize into groups upon photoirradiation. The groups of transporters load and transport cargo, and cargo unloading is achieved by dissociating the groups into single microtubules. The group formation permits the loading and transport of cargoes with larger sizes and in larger numbers over long distances compared with single transporters. We also demonstrate that cargo can be collected at user-determined locations defined by ultraviolet light exposure. This work demonstrates cooperative task performance by molecular machines, which will help to construct molecular robots with advanced functionalities in the future.

DOI： 10.1126/scirobotics.abm0677

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Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

Hyaluronic acid (HA)-coated biodegradable polymeric micelles were developed as nanoparticulate vaccine delivery systems to establish an effective nasal vaccine.

DOI： 10.1039/d1bm01985f

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Publishing type：Research paper (scientific journal)  

DOI： 10.1080/14686996.2021.1938212

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

A tripod molecule incorporating a C-60 photocatalyst into a rigid scaffold with disulfide legs was designed and synthesized for the stable and robust attachment of C-60 onto an Au-coated atomic force microscope (AFM) tip. The "tripod-C-60" was immobilized onto the tip by forming S-Au bonds in the desired orientation and a dispersed manner, rendering it suitable for the oxidation and scission of single molecules on a countersurface, thereby functioning as "molecular shears". A DNA origami with a well-defined structure was chosen as the substrate for the tip-induced oxidation. The gold-coated, C-60-functionalized AFM tip was used for both AFM imaging and oxidation of DNA origami upon visible-light irradiation. The localized and temporally controlled oxidative damage of DNA origami was successfully performed at the single-molecule level via singlet-oxygen (O-1(2)) generation from the immobilized C-60 on the AFM tip. This oxidative damage to DNA origami can be carried out under ambient conditions in a fluid cell at room temperature, rendering it well-suited for the manipulation of a variety of species on surfaces via a spatially and temporally controlled oxidation reaction triggered by O-1(2) locally generated from the immobilized C-60 on the AFM tip.

DOI： 10.1021/acsnano.1c04953

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Publishing type：Research paper (scientific journal)   Publisher：Elsevier BV  

DOI： 10.1016/j.actbio.2021.08.033

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Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society ({ACS})  

DOI： 10.1021/acsabm.0c01467

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japanese Society for Engineering Education  

DOI： 10.4307/jsee.69.4_31

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Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry (RSC)  

<p>Application of split G-quadruplex as DNAzyme reporter system for DNA sensing.</p>

DOI： 10.1039/D0RA05439A

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI  

This study introduces a modeling method for a supermolecular structure of microtubules for the development of a force generation material using motor proteins. 3D imaging by confocal laser scanning microscopy (CLSM) was used to obtain 3D volume density data. The density data were then interpreted by a set of cylinders with the general-purpose 3D modeling software Blender, and a 3D network structure of microtubules was constructed. Although motor proteins were not visualized experimentally, they were introduced into the model to simulate pulling of the microtubules toward each other to yield shrinking of the network, resulting in contraction of the artificial muscle. From the successful force generation simulation of the obtained model structure of artificial muscle, the modeling method introduced here could be useful in various studies for potential improvements of this contractile molecular system.

DOI： 10.3390/mi11090844

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Nanoparticles exhibit a number of unique properties such as localized surface plasmon resonance (LSPR). As this LSPR is sensitive to geometrical or spatial conditions, the arrangement of nanoparticles, in particular the active arrangement of plasmonic structures, is an important issue. In this study, gold nanorod (GNR) arrays were prepared by GNR attachment on anionic polymer (DNA) brushes via electrostatic interactions and their stimuli-responsive changes in orientationwere investigated. As a result, the orientation of GNR arrays on DNA brushes reversibly changed by the modulation of electrostatic interactions between GNRs and polymers via changes in the solution pH. As these extensive GNR arrays are prepared via easy bottom-up processes, GNR surface properties are easily tuned by simple modification, and DNAs could be replaced with various synthetic polymers, we believe that this study will lead to the development of nextgeneration materials and devices with actively tunable structures.

DOI： 10.1039/d0na00315h

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

A promising approach for the regeneration of tissues or organs with three-dimensional hierarchical structures is the preparation of scaffold-cell complexes that mimic these hierarchical structures. This requires an effective technique for immobilizing cell-specific ligands at arbitrarily chosen positions on matrices. Here, we report a versatile system for arranging cell-specific ligands onto desired compartments of biodegradable matrices for site-selective cell arrangement. We utilized the specific binding abilities of specific DNAs, immobilizing them as tags to arrange cell-recognition ligands at desired areas of the matrices by specific binding with cell-recognition ligand-DNA conjugates. We synthesized poly(L-lactide) (PLLA), a biodegradable polymer, with an oligo-DNA (trimer of deoxyguanosine: dG(3)) attached via a poly(ethylene glycol) (PEG) spacer to generate dG(3)-PEG-b-PLLA. The peptides Arg-Gly-Asp-Ser (RGDS) and Arg-Glu-Asp-Val (REDV) were chosen as cell-recognition ligands and were attached to an adapter DNA (aDNA), which can specifically bind to the dG(3) moiety through G-quadruplex formation. The obtained dG(3)-PEG-b-PLLA was deposited on a small spot of the PLLA film, and the aDNA RGDS or aDNA REDV conjugate was added on the film to immobilize these ligands at the spot. We confirmed the specific adhesion of L929 cells (a mouse fibroblast cell line) and human umbilical vein endothelial cells (HUVECs) on the small areas coated with dG(3)-PEG-b-PLLA in the presence of aDNA-RGDS and aDNA-REDV, respectively, even after applying shear stress by flowing medium across the spot. Cell-specific attachment of the target cells was effectively achieved in a spatially controlled manner. This technique has the potential for the construction of cell-scaffold complexes that mimic the hierarchical structures of natural organs and may represent a breakthrough in realizing regenerative medicine and tissue engineering of complex organs.

DOI： 10.1021/acs.biomac.0c00814

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Small-caliber artificial blood vessels with inner diameters of smaller than 4 mm have not been put into practical use because of early thrombus formation and graft occlusion. To realize small-caliber artificial blood vessels with anti-thrombus property and long-term patency, one of the promising approaches is endothelialization of the lumen by tissue engineering approaches. Integrin alpha 4 beta 1 on the endothelial cell membrane is known to act as a receptor for Arg-Glu-Asp-Val (REDV) tetra-peptide, and this peptide can be used as a specific ligand to introduce endothelial cell attachment onto the surfaces of polymer scaffold. In this study, biodegradable polymer surface immobilizing REDV peptide were prepared, and the specific attachment of endothelial cells on it was investigated as a preliminary study for tissue-engineered small-caliber blood vessels in a future application. We synthesized copolymer of epsilon-caprolactone and depsipeptide having reactive carboxylic acid side-chain groups (PGDCL), and REDV peptide was attached to the copolymer to give PGDCL-REDV. The attachment of human umbilical vein endothelial cells (HUVECs) were investigated for the blend polymer film prepared by mixing PGDCL and PGDCL-REDV. The obtained blend polymer films exhibited sequence- and cell-specific HUVECs attachment through REDV peptide recognition. This technique should be useful not only to obtain artificial blood vessels which induce endothelialization and but also to provide biodegradable scaffolds with specific ligands immobilized surfaces for tissue regeneration.

DOI： 10.1080/09205063.2020.1762325

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Thermal properties and degradation of enantiomeric random copolyesteramides poly(L-lactic acid-co-i.alanine) [P(LLA-LAL)] and poly(D-lactic acid-co-o-alanine) [P(DLA-DAL)] copolymers with wide alanine unit content ranges from 0 to 21 and 22 mol% were investigated by differential scanning calorimetry and themogravimetry. The total enthalpy of cold crystallization enthalpy and melting enthalpy as an indicator of crystallinity decreased with a decrease in lactic acid unit content or an increase in alanine unit content. Equilibrium melting temperature values of a-form homo-crystallites for the unblended samples decreased with an increase in alanine unit content (1573-179.6 degrees C) and those of 6-form homocrystallites for the unblended L100 and D100 (190.7 and 185.1 degrees C) were much higher than the reported values (both 172.8 degrees C, Polymer 2017, 9, 625). Thermal stability was enhanced by enantiomeric polymer blending, although thermal degradation was accelerated by incorporated alanine units. The activation energy for thermal degradation (dE td ) of the blend samples decreased with an increase in alanine unit content, whereas that of the unblended samples showed complicated dependence on alanine unit content and became maximum at alanine unit contents of 21 and 22 mol%. The blend samples had higher dE t d values comparted to those of the unblended samples, except for the alanine unit contents of 21 and 22 mol%. The reason for the high dE t d values of the unblended samples compared with that of the blend sample at the alanine unit contents of 21 and 22 mol% is discussed. (C) 2019 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.polymdegradstab.2019.109047

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Publishing type：Research paper (scientific journal)   Publisher：Wiley  

DOI： 10.1002/pcr2.10094

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Other Link： https://onlinelibrary.wiley.com/doi/full-xml/10.1002/pcr2.10094

Authorship：Last author,　Corresponding author   Publishing type：Research paper (scientific journal)  

DOI： 10.3390/polym11101607

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Authorship：Last author,　Corresponding author   Publishing type：Research paper (scientific journal)  

DOI： 10.1149/2.0441909jes

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Publishing type：Research paper (scientific journal)  

DOI： 10.1177/2472555218791743

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Recently we demonstrated swarming of a self-propelled biomolecular motor system microtubule (MT)-kinesin where interactions among thousands of motile MTs were regulated in a highly programmable fashion by using DNA as a processor. However, precise control of this potential system is yet to be achieved to optimize the swarm behavior. In this work, we systematically controlled swarming of MTs on kinesin adhered surface by different physicochemical parameters of MT-kinesin and DNA. Tuning the length of DNA sequences swarming was precisely controlled with thermodynamic and kinetic feasibility. In addition, swarming was regulated using different concentration of DNA crosslinkers. Reversibility of swarming was further controlled by changing the concentration of strand displacement DNA signal allowing dissociation of swarm. The control over the swarm was accompanied by variable stiffness of MTs successfully, providing translational and circular motion. Moreover, the morphology of swarm was also found to be changed not only depending on the stiffness but also body length of MTs. Such detail study of precise control of swarming would provide new insights in developing a promising molecular swarm robotic system with desired functions.

DOI： 10.1038/s41598-018-30187-1

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：The Electrochemical Society  

DOI： 10.1149/MA2018-03/1/3

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Authorship：Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：The Electrochemical Society  

DOI： 10.1149/MA2018-03/1/94

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Authorship：Last author,　Corresponding author   Publishing type：Research paper (scientific journal)   Publisher：The Electrochemical Society  

DOI： 10.1149/MA2018-03/1/89

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Nanogels, nanometer-sized hydrogel particles, have great potential as drug delivery carriers. To achieve effective drug delivery to the active sites in a cell, control of intracellular traffic is important. In this study, we prepared nanogels composed of dextran with oligolactide (OLA) chains attached via disulfide bonds (Dex-g-SS-OLA) that collapse under the reductive conditions of the cytosol to achieve efficient drug delivery. In addition, we introduced galactose (Gal) residues on the nanogels, to enhance cellular uptake by receptor-mediated endocytosis, and secondary oligo-amine (tetraethylenepentamine) groups, to aid in escape from endosomes via proton sponge effects. The obtained Dex-g-SS-OLA with attached Gal residues and tetraethylenepentamine (EI4) groups, EI4/Gal-Dex-g-SS-OLA, formed a nanogel with a hydrodynamic diameter of ca. 203 nm in phosphate-buffered solution. The collapse of the EI4/Gal-Dex-g-SS-OLA nanogels under reductive conditions was confirmed by a decrease in the hydrodynamic diameter in the presence of reductive agents. The specific uptake of the hydrogels into HepG2 cells and their intercellular behavior were investigated by flow cytometry and confocal laser scanning microscopy using fluorescence dye-labeled nanogels. Escape from the endosome and subsequent collapse in the cytosol of the EI4/Gal-Dex-g-SS-OLA were observed. These biodegradable nanogels that collapse under reductive conditions in the cytosol should have great potential as efficient drug carriers in, for example, cancer chemotherapy.

DOI： 10.3390/ijms19061606

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Authorship：Last author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society  

A new pH-responsive hydrogel biomaterial, that is composed of solely two popular biocompatible materials, oligodeoxynucleotides (ODN) and polyethylene glycol (PEG) have been prepared. Merely five deoxycytidine residues were elongated to the ends of linear or 4-arm PEG in ×1000 larger scale than conventional systems by using liquid-phase DNA synthesis technique, and applied them as a macromonomer for the preparation of hydrogels. The syntheses of the conjugates are simply elongating ODN onto the ends of PEG as a semisolid phase substrate using standard phosphoramidite chemistry. The resulting dC5-PEG conjugates gave quite stable and stiff hydrogels triggered by the formation of a unique DNA quadruplex, i-motif. Introduction of only one chemical linkage between two linear conjugates resulted in unexpectedly high thermal stabilities for the melting temperatures of i-motifs themselves. Nonlinearly improved rheological properties compared to the original linear conjugates were also observed, probably because of topological entanglement between macromonomers of fused circles.

DOI： 10.1021/acsmacrolett.8b00063

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：Royal Society of Chemistry  

α-Hydroxy acid and α-amino acid-derived poly(l-lactic acid-co-l-alanine)s and poly(d-lactic acid-co-d-alanine)s with different alanine unit contents were synthesized by copolymerization of l-lactide and (3S,6S)-3,6-dimethyl-morpholine-2,5-dione and of d-lactide and (3R,6R)-3,6-dimethyl-morpholine-2,5-dione, respectively. The effects of the incorporated alanine units in lactic acid units or amide linkages in ester linkages on the crystallization behavior of solution- and melt-crystallized 50/50 blended samples as well as that of solution- and melt-crystallized nonblended samples were investigated. This article reports for the first time a stereocomplex (SC) formation between enantiomeric random copolyesteramides poly(lactic acid-co-alanine)s with ester and amide linkages. The solution-crystallized nonblended samples crystallized in α- or δ-form homo-crystallites for an l-alanine unit content up to 6 mol% or a d-alanine unit content up to 3 mol%, whereas all the melt-crystallized samples crystallized in α- or δ-form homo-crystallites for the l- or d-alanine unit content at least up to 12 and 13 mol%. In contrast, the solution-crystallized blended samples with the alanine unit contents of 0-13 mol% and the melt-crystallized blended samples with the alanine unit contents of 4-13 mol% crystallized only in SC crystallites, whereas the melt-crystallized blended samples with an alanine unit content of 0 mol% [i.e., poly(l-lactic acid)/poly(d-lactic acid) blends] crystallized in both SC crystallites and homo-crystallites. The alanine units of melt-crystallized nonblended samples were incorporated into homo-crystalline regions, whereas those of solution-crystallized nonblended samples were excluded from homo-crystalline regions. In contrast, the alanine units of solution-crystallized blended samples were incorporated into SC crystalline regions, whereas those of melt-crystallized blended samples were excluded from SC crystalline regions.

DOI： 10.1039/c7py02024d

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)  

DOI： 10.15406/mojps.2017.01.00033

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Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

DOI： 10.3390/gels3040038

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Authorship：Lead author   Publishing type：Research paper (scientific journal)   Publisher：American Chemical Society ({ACS})  

DOI： 10.1021/acsomega.7b00966

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

Amphiphilic triblock copolymers of poly(ethylene glycol) (PEG) and aliphatic polyesters such as poly(e-caprolactone-co-glycolide) (PCGA) are typical examples of thermogelling polymers. In the gelation mechanism of these polymers, polymer chain transfer between the micelles, and subsequent aggregation of the micelles are important steps. We previously reported IP systems exhibiting temperature-responsive irreversible sol-gel transition that formed covalently cross-linked hydrogels. The IP formulation prepared by the 'freeze-dry with PEG/dispersion' method (D-sample) retained its sol state at r.t. longer than a formulation prepared by the usual dissolution method (S-sample). We hypothesized that polymer chain transfer between micelles was suppressed in the D-samples, because the micelle cores were in a solid-like state. In this study, we investigated polymer chain transfer by the fluorescence resonance energy transfer (FRET) method to reveal its role in the sol-to-gel transition. We synthesized a triblock copolymer of PCGA and PEG (tri-PCG) with attached naphthalene or dansyl groups at termini, tri-PCG-nap and tri-PCG-dan, as FRET donors and acceptors, respectively. The FRET behavior of the mixture of tri-PCG-nap/tri-PCG micelles and tri-PCG-dan/tri-PCG micelles was investigated. It was revealed that polymer chain transfer between micelles was strongly accelerated at the gelation temperature, and polymer chain transfer in D-samples was suppressed compared to S-samples.

DOI： 10.1038/pj.2017.33

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Language：English   Publisher：(一社)日本生物物理学会  

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Language：English   Publisher：(一社)日本生物物理学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Here, we report biodegradable temperature-triggered covalent gelation systems exhibiting a longer and controllable duration time of the gel state by a "mixing strategy" utilizing a thiol-ene reaction. We synthesized a tri-block copolymer of poly(caprolactone-co-glycolic acid) and PEG (tri-PCG) as a temperature-responsive injectable polymer (IP) and attached acryloyl groups on both termini (tri-PCG-Acryl). A tri-PCG micelle solution containing hydrophobic hexa-functional polythiol (Solution-A) and a tri-PCG-Acryl micelle solution (Solution-B) were mixed together. After mixing, the solution was still in the sol state at r.t., but exhibited an irreversible sol-to-gel transition in response to temperature. The duration time of the gel state while soaking in PBS could be altered from 1 day to 93 days by changing the mixing ratio of Solution-A/B. The physical strengths of the hydrogels were also controllable by changing the mixing ratio. The IP system showed good biocompatibility and a long duration time of the gel state after subcutaneous implantation.

DOI： 10.1039/c7bm00357a

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Significant enhancement of single-molecular binding to a miRNA target and bidentate and asymmetric conjugation of two distinct thiolated DNA strands to single gold nanoparticles (AuNPs) were visibly demonstrated, by introducing two groups of ligands into our nanomechanical DNA origami devices (DNA pliers) to construct allosterically controllable systems.

DOI： 10.1039/c7cc03991c

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

A split aptamer for adenosine triphosphate (ATP) was embedded as a recognition unit into two levers of a nanomechanical DNA origami construct by extension and modification of selected staple strands. An additional optical module in the stem of the split aptamer comprised two different cyanine styryl dyes that underwent an energy transfer from green (donor) to red (acceptor) emission if two ATP molecules were bound as target molecule to the recognition module and thereby brought the dyes in close proximity. As a result, the ATP as a target triggered the DNA origami shape transition and yielded a fluorescence color change from green to red as readout. Conventional atomic force microscopy (AFM) images confirmed the topology change from the open form of the DNA origami in the absence of ATP into the closed form in the presence of the target molecule. The obtained dosed/open ratios in the absence and presence of target molecules tracked well with the fluorescence color ratios and thereby validated the bicolor fluorescence readout. The correct positioning of the split aptamer as the functional unit farthest away from the fulcrum of the DNA origami was crucial for the aptasensing by fluorescence readout. The fluorescence color change allowed additionally to follow the topology change of the DNA origami aptasensor in real time in solution. The concepts of fluorescence energy transfer for bicolor readout in a split aptamer in solution, and AFM on surfaces, were successfully combined in a single DNA origami construct to obtain a bimodal readout. These results are important for future custom DNA devices for chemical biological and bioanalytical purposes because they are not only working as simple aptamers but are also visible by AFM on the single-molecule level.

DOI： 10.1021/acs.nanolett.7b00159

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Biodegradable injectable polymer (IP) systems exhibiting temperature-responsive sol-to-gel transitions between room temperature and body temperature have the potential for use in biomedical applications. However, gelation of such IP systems is a reversible process through physical cross-linking, and the hydrogels thus formed are likely to revert to the sol state under highly wet conditions after injection. In this study, a biodegradable IP system exhibiting temperature responsive irreversible sol-to-gel transition by covalent bond formation was developed by simple mixing of polymers. A triblock copolymer of poly(caprolactone-co-glycolic acid) and poly(ethylene glycol) (tri-PCG) and tri-PCG with attached succinimide ester groups at both termini (tri-PCG-SA-OSu) were prepared and mixed together with a water-soluble polyamine (typically poly-L-lysine). The obtained IP formulation was in the sol state after mixing, but exhibited a rapid sol-to-gel transition within 30 s upon increasing the temperature to 37 degrees C. Once formed, the hydrogel did not revert to the sol state, even after cooling to 4 degrees C, because of the formation of covalent bonds upon transition. The obtained hydrogel soaked in phosphate buffered saline (PBS) exhibited a significantly longer duration time of the gel state. This IP system exhibiting a rapid and irreversible sol-to-gel transition is convenient for medical professionals and possesses great potential for use in biomedical devices for clinical applications such as drug delivery systems and antiadhesive materials.

DOI： 10.1021/acsbiomaterials.6b00581

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

Aqueous solutions of biodegradable polymers exhibiting sol-to-gel transitions in response to external stimuli such as temperature and pH are expected to be used as injectable polymers (IPs) for biomedical applications. In this study, we prepared novel biodegradable temperature-responsive IP systems providing variable gel-forming pH regions. We synthesized PCGA-b-PEG-b-PCGA (tri-PCG) and attached carboxylic acid or primary amine groups on both termini, tri-PCG-COOH and tri-PCG-NH 2, and investigated the temperature-responsive sol-to-gel transition behavior of the mixtures of these two copolymers at various pHs. We found that the gel-forming pH region of the mixed system could be easily controlled by simply changing the mixing ratios of these polymers.

DOI： 10.1080/09205063.2017.1304170

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS LTD  

On clinical application of biodegradable injectable polymer (IP) systems, quick extemporaneous preparation of IP formulations and longer duration time gel state after injection into the body are the important targets to be developed. Previously, we had reported temperature-responsive covalent gelation systems via bio-orthogonal thiol-ene reaction by mixing strategy' of amphiphilic biodegradable tri-block copolymer (tri-PCG) attaching acryloyl groups on both termini (tri-PCG-Acryl) with reactive polythiol. In other previous works, we found freeze-dry with PEG/dispersion' method as quick extemporaneous preparation method of biodegradable IP formulations. In this study, we applied this quick preparative method to the temperature-triggered covalent gelation system. The instant formulation (D-sample) could be prepared by freeze-dry with PEG/dispersion' just mixing of tri-PCG-Acryl micelle dispersion and tri-PCG/DPMP micelle dispersion with PEG, that can be prepared in 30s from the dried samples. The obtained D-sample showed irreversible gelation and long duration time of gel state, which was basically the same as the formulations prepared by the usual heating dissolution method (S-sample). Interestingly, the D-sample could maintain its sol state for a longer time (24h) after preparing the formulation at r.t. compared with the S-sample, which became a gel in 3h after preparing. The IP system showed good biocompatibility and long duration time of the gel state after subcutaneous implantation. These characteristics of D-samples, quick extemporaneous preparation and high stability in the sol state before injection, would be very convenient in a clinical setting.

DOI： 10.1080/09205063.2017.1330114

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：AMER CHEMICAL SOC  

Poly(ethylene glycol) (PEG) is widely used as a biomedical material because it possesses the highest level of biocompatibility among synthetic polymers. However, PEG is water-soluble and non-biodegradable. To provide biodegradable water-insoluble bulk materials possessing the biocompatibility of PEG, water-insoluble poly(ether-ester)s were synthesized by thiol-ene polyaddition of poly(ethylene glycol) diacrylates (PEGDA) and alkyl dithiols (ADTs). Among them, P(PEG-DDT) prepared from PEGDA and decanedithiol (DDT) film cast on a glass substrate possessed temperature-responsive changes only when immersed in water. The P(PEG-DDT) film was transparent in a water bath at 0 degrees C, but become opaque after subsequent soaking in a hot water bath at 40-70 degrees C. The mechanism was examined by measuring transmittance changes in response to temperature, differential colorimetry, and air contact angle of the film in water. Water-insoluble poly(ether-ester)s exhibiting temperature-responsiveness have potential, not only as new bulk-state biomaterials with PEG-like biocompatibility but also as new environmentally friendly temperature-responsive materials.

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Language：English   Publisher：(一社)日本生物物理学会  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCI LTD  

Ethylene glycol (EG) and succinic anhydride (SA)-based 2-armed PLLA and PDLA correspondingly with tail-to-tail (T-T) and head-to-head (H-H) architectures, together with SA-based linear 2-armed stereo diblock copolymer, were synthesized and the SC crystallization and homo-crystallization behavior of blends of 2-armed PLLA and PDLA with various combinations of molecular architectures, together with that of neat polymers, were investigated. The crystallizability was higher for SC crystalline samples than for homo-crystalline samples during solvent evaporation and slow cooling from the melt. The hydrogen bonds of hydroxyl terminals and/or low molecular weight of EG-based polymer rather than specific chain directional architecture or its combination disturbed and delayed the crystallization, lowering the crystallization temperature (T-c), crystalline], the reciprocal of experimental crystallization half time [1/t(c)(1/2) (exp)], spherulite growth rate (G), enthalpy of crystallization (Delta(Hc)) for 1st cooling, and total enthalpy of cold crystallization and melting [Delta H(tot)] for 2nd heating of both SC crystalline and homocrystalline samples, the melting temperature (T-m) for 1st and 2nd heating, nucleus density and the degree of lamella orientation of spherulites of SC crystalline samples. The opposite chain directional architectures of polymers in blends should have increased Delta H(tot) for 1st heating, Delta H-c for 1st cooling, Delta H(tot) for 2nd heating, and G of SC crystalline samples. The effects of hydrogen bonds of hydroxyl terminal groups, M-n (or M-n per one arm or block), and chain directional combination were determined by the crystallization temperature range and the presence or absence of a solvent. The Tm values of SC crystalline samples were determined by M-n (or M-n per one arm or block), whereas those of homocrystalline samples did not show clear dependence on M-n (or M-n per one arm or block) values per one arm, hydroxyl terminal groups (hydrogen bonding), or chain direction. The intermolecular SC crystallization in the enantiomeric polymer blends was favored compared with intramolecular SC crystallization in the stereo diblock copolymer. (C) 2016 Elsevier Ltd. All rights reserved.

DOI： 10.1016/j.polymer.2016.04.049

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

DNA aptamers have potential for disease diagnosis and as therapeutics, particularly when interfaced with programmable molecular technology. Here we have combined DNA aptamers specific for the malaria biomarker Plasmodium falciparum lactate dehydrogenase (PfLDH) with a DNA origami scaffold. Twelve aptamers that recognise PfLDH were integrated into a rectangular DNA origami and atomic force microscopy demonstrated that the incorporated aptamers preserve their ability to specifically bind target protein. Captured PfLDH retained enzymatic activity and protein-aptamer binding was observed dynamically using high-speed AFM. This work demonstrates the ability of DNA aptamers to recognise a malaria biomarker whilst being integrated within a supramolecular DNA scaffold, opening new possibilities for malaria diagnostic approaches based on DNA nanotechnology.

DOI： 10.1038/srep21266

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DOI： 10.1080/14686996.2016.1189798

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media {SA}  

DOI： 10.3389/conf.fbioe.2016.01.01123

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Publishing type：Research paper (scientific journal)   Publisher：Frontiers Media {SA}  

DOI： 10.3389/conf.fbioe.2016.01.01115

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Bottom-up fabrication techniques are expected to alleviate the limitations of top-down fabrication. Bottom-up fabrication requires self-assembling facilities to construct complex structures including DNA nanostructures, DNA robots, further molecular robots, and so on. DNA origami is one of buttom-up fabrication techniques. In this paper, we focus on the automatic recognition of flexible DNA origami named "DNA pliers" in AFM (atomic force microscopy) image. Auto recognition of DNA pliers is challenging and necessary since DNA pliers can have several forms: parallel, cross, and anti-parallel forms, depending on hinge angles. Our method uses the information of the curvature scale space method and convexity-concavity detection extracted from DNA pliers. The experiments show that the combination of the curvature scale space method and convexity-concavity detection can work well for DNA pliers recognition if appropriate contour information for the DNA pliers is available from an AFM image.

DOI： 10.1007/s00354-015-0305-4

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

A box-shaped' three-dimensional (3D) DNA origami of similar to 40-nm dimensions was selectively formed by closing a symmetric open motif with three orthogonal faces. This 3D DNA origami was used as an intelligent nano-container to encapsulate exactly one 10-nm gold nanoparticle (AuNP). AuNPs were functionalized with thiol-modified DNA strands and attached to one of the faces of the open motif, which was designed to be an interior surface of the box and decorated with three complementary strands. The open motif was then closed into the box shape as triggered by the addition of DNA strands joining the remaining edges. An examination of the suitable folding path of an M13 scaffold using fluorescently labeled staple strands revealed that the flexibility at the hinge was essential for the efficient closing of the DNA origami container. Atomic force microscope and transmission electron microscope imaging of agarose-gel-purified complexes clearly showed the successful encapsulation of one AuNP inside the shell.

DOI： 10.1038/pj.2014.128

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-BLACKWELL  

We propose a macromolecular prodrug strategy of an injectable polymer (IP) system for continuous and sustained release of water-soluble low-molecular-weight drugs. A biodegradable graft copolymer-type IP covalently immobilizing model drugs via hydrolyzable ester bonds was synthesized through the coupling reaction of poly(depsipeptide-co-dl-lactide), P(DG-dl-LA), having reactive carboxylic acid side-chain groups with the amino derivative of a model drug (levofloxacin [LEV]) and monomethoxy-poly(ethylene glycol) (PEG). The solution of the obtained graft copolymer-type IP/model drug conjugate exhibited a temperature-responsive sol-to-gel transition between room temperature and body temperature in phosphate buffer solution, similar to P(GD-dl-LA)-g-PEG without LEV. The immobilization of the LEV molecule onto P(DG-dl-LA)-g-PEG did not have a significant influence on the sol-to-gel transition behavior, physical properties, or in vitro degradation rates of the hydrogels. The in vitro release of LEV derivatives from the P(DG-dl-LA)-g-PEG/LEV hydrogel in phosphate buffer solution was continuous for 11weeks, which corresponded to the degradation period of the hydrogel, and slower than that from the control hydrogels prepared from P(DG-dl-LA)-g-PEG and PLGA-b-PEG-b-PLGA that physically entrapped LEV molecules. These results suggest that the covalent attachment strategy is effective in achieving sustained release of low-molecular-weight drugs in IP systems and can be applied to drug delivery devices for highly bioactive drugs. Copyright (c) 2014 John Wiley & Sons, Ltd.

DOI： 10.1002/pat.3265

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

Single-molecule pH sensors have been developed by utilizing molecular imaging of pH-responsive shape transition of nanomechanical DNA origami devices with atomic force microscopy (AFM). Short DNA fragments that can form i-motifs were introduced to nanomechanical DNA origami devices with pliers-like shape (DNA Origami Pliers), which consist of two levers of 170-nm long and 20-nm wide connected at a Holliday-junction fulcrum. DNA Origami Pliers can be observed as in three distinct forms; cross, antiparallel and parallel forms, and cross form is the dominant species when no additional interaction is introduced to DNA Origami Pliers. Introduction of nine pairs of 12-mer sequence (5'-AACCCCAACCCC-3'), which dimerize into i-motif quadruplexes upon protonation of cytosine, drives transition of DNA Origami Pliers from open cross form into closed parallel form under acidic conditions. Such pH-dependent transition was clearly imaged on mica in molecular resolution by AFM, showing potential application of the system to single-molecular pH sensors.

DOI： 10.3390/s141019329

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：NATURE PUBLISHING GROUP  

DOI： 10.1038/pj.2014.30

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DOI： 10.1039/c4nr01598c

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ACADEMIC PRESS INC ELSEVIER SCIENCE  

Precise structure switching between all of the three forms of three-state nanomechanical DNA origami devices has been accomplished. A nanomechanical DNA origami device called DNA origami pliers, which consists of two levers of 170-nm long, 20-nm wide, and 2-nm thick connected at a Holliday-junction fulcrum, takes three conformations: closed parallel, closed antiparallel, and open cross forms. They were previously applied to construct detection systems for biomolecules in single-molecular resolution by observing the structure switching between cross form and one of the other two forms under atomic force microscope (AFM). We redesigned DNA origami pliers in this study to let them freely switch between all of the three states including parallel-antiparallel direct switching without taking cross form. By the addition of appropriate switcher strands to the solution, hybridization and dehybridization of particular binder strands that fix the levers into predetermined state were selectively triggered as programmed in their sequence. Circuit structure switching through all of the three states in both of the two opposite direction was even successful with the new design. (C) 2013 Elsevier Inc. All rights reserved.

DOI： 10.1016/j.ymeth.2013.11.003

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DOI： 10.1080/09205063.2013.869150

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Authorship：Lead author,　Corresponding author   Publishing type：Research paper (scientific journal)  

DOI： 10.1021/ar400328v

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：HINDAWI PUBLISHING CORPORATION  

We synthesized series of amphiphilic AB-type block copolymers having systematic variation in the core-forming segments using poly(lactide-co-depsipeptide)s as a hydrophobic segment and prepared polymeric micelles using the block copolymers, PEG-b-poly(lactide-co-depsipeptide). We then discussed the relationship between the core-forming segment structure and drug loading efficiency for the polymeric micelles. PEG-b-poly(lactide-co-depsipeptide) s, PEG-b-PLGL containing L-leucine (Leu), and PEG-b-PLGF containing L-phenylalanine (Phe), with similar molecular weights and various mole fractions of depsipeptide units, were synthesized. Polymeric micelles entrapping model drug (fluorescein, FL) were prepared using these copolymers. As a result, PEG-b-poly(lactide-co-depsipeptide) micelles showed higher drug loading compared with PEG-b-PLLA and PEG-b-PDLLA as controls. The drug loading increased with increase in the mole fraction of depsipeptide unit in the hydrophobic segments. The introduction of aliphatic and aromatic depsipeptide units was effective to achieve higher FL loading into the micelles. PEG-b-PLGL micelle showed higher drug loading than PEG-b-PLGF micelle when the amount of FL in feed was high. These results obtained in this study should be useful for strategic design of polymeric micelle-type drug delivery carrier with high drug loading efficiency.

DOI： 10.1155/2014/579212

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Language：English   Publishing type：Research paper (international conference proceedings)   Publisher：TRANS TECH PUBLICATIONS LTD  

Starburst triblock copolymers consisting of 8-arm poly(ethylene glycol) (8-arm PEG), poly(L-lactide) (PLLA) or its enantiomer poly(D-lactide) (PDLA) and terminal PEG, 8-arm PEG-b-PLLA-b-PEG (Stri-L) and 8-arm PEG-b- PDLA-b-PEG (Stri-D), were synthesized. An aqueous solution of a 1:1 mixture (Stri-Mix) of Stri-L and Stri-D assumed a sol state at room temperature, but instantaneously formed a physically cross-linked hydrogel in response to increasing temperature. The resulting hydrogel exhibited a high storage modulus at 37 degrees C. The rapid temperature-triggered hydrogel formation, high mechanical strength, and degradation behavior render this polymer system suitable for use in injectable drug delivery system or a biodegradable scaffold for tissue engineering.

DOI： 10.4028/www.scientific.net/AST.86.9

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

DOI： 10.1002/smll.201200092

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Authorship：Lead author   Language：English   Publisher：NATURE PUBLISHING GROUP  

The rapid development of DNA nanotechnology has enabled the precise bottom-up integration of metal nanoparticles (NPs) on a nanometer scale. The recent introduction of the DNA origami technique has facilitated even more complicated control of the positioning of not only 2 dimensional (D) but also 3D structures. The basic idea and recent distinctive examples of such metal NP arrays on DNA nanostructure are briefly reviewed. Polymer Journal (2012) 44, 452-460; doi:10.1038/pj.2012.38; published online 28 March 2012

DOI： 10.1038/pj.2012.38

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：MDPI AG  

A new simple scheme for constructing recombinant vectors that does not require any restriction enzyme, ligase, or any other special enzyme treatment has been developed. By using caged primers in PCR, unnatural sticky-ends of any sequence, which are sufficiently long for ligation-independent cloning (LIC), are directly prepared on the product after a brief UVA irradiation. Target genes and vectors amplified by this light-assisted cohesive-ending (LACE) PCR join together in the desired arrangement in a simple mixture of them, tightly enough to be repaired and ligated in competent cells.

DOI： 10.3390/molecules17010328

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Language：English   Publishing type：Research paper (international conference proceedings)  

We propose versatile sensing systems for a variety of chemical and biological targets at molecular resolution. We have designed functional nanomechanical DNA origami devices that can be used as "single-molecule beacons", which consist of two levers approximately 170 nm long connected at a fulcrum. Various single-molecule inorganic/organic targets ranging from metal ions to proteins as well as a unique binding event of a nucleic acid analogue can be visually detected on AFM by a shape transition of the origami devices. © 2012 IEEE.

DOI： 10.1109/NEMS.2012.6196783

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Invasive binding event of PNA into DNA duplex was clearly observed both by atomic force microscope (AFM) imaging and electrophoretic mobility shift assay (EMSA) with the aid of nanomechanical DNA origami devices as 'single-molecule' visual probes, showing their potential as universal platform for the analysis of PNA invasion.

DOI： 10.1039/c2cc36358e

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Photoresponsive systems for site-selective RNA scission have been prepared by combining Lu(III) ions with acridine/azobenzene dual-modified DNA. The modified DNA forms a heteroduplex with substrate RNA, and the target phosphodiester linkages in front of the acridine residue is selectively activated so that Lu(III) ion rapidly cleaves the linkage. Azobenzene residue introduced adjacent to the acridine residue acts as a photoresponsive switch, which triggers the site-selective scission upon UV irradiation. A trans isomer of azobenzene efficiently suppresses the scission, whereas the cis isomer formed by UV irradiation hardly affects the scission. As a result, 1.7-2.4-fold acceleration of the cleavage was achieved simply by irradiating UV for 3 min to the mixture prior to the reaction. Considering the yield of photoisomerization, the intrinsic activity of a cis isomer is up to 14.5-fold higher than that of the trans isomer. © 2011 Akinori Kuzuya et al.

DOI： 10.4061/2011/162452

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Language：Japanese   Publisher：The Robotics Society of Japan  

DOI： 10.7210/jrsj.28.1155

CiNii Books

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Other Link： https://jlc.jst.go.jp/DN/JALC/00361732299?from=CiNii

Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

DOI： 10.1002/smll.201001484

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Desired enzyme nanoarrays patterned on a DNA origami scaffold were selectively isolated by affinity tag purification from a pool of differently patterned nanoarrays, and their enzymatic activity was successfully confirmed. As few as 12 histidine residues were enough to hold a huge complex of DNA origami with multiple proteins, 260 nm in length and 5.2 MDa in molecular weight, to an immobilized metal affinity resin.

DOI： 10.1021/ja104702q

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Rectangular DNA motifs, which each have a built-in cavity in the middle, were prepared by bundling nine DNA helices into a U-shaped tile first and then assembling two of them together. The cavity was modified with two or three biotin molecules and was used as a nanometer-sized well to capture a single streptavidin (SA) tetramer size-selectively. Selective, one-step formation of asymmetric secondary or tertiary SA/DNA complexes via bidentate or tridentate capture have been shown by analyses of the complexes with denaturing polyacrylamide gel electrophoresis. When biotinylated DNA was simply added to the solution of SA, only symmetric SA/DNA complexes were formed as a mixture of primary to quaternary complexes, depending on the amount of DNA. However, when the DNA motif was preformed prior to SA addition, the asymmetric secondary complex was preferentially formed. The yield of the asymmetric secondary complex was ca. 50% when biotins were tethered to the two-turn well (6.8 nm wide) via 2.3 nm linkers, whereas the yield of the mixture of symmetric and asymmetric secondary complexes was only 7% for the reaction in bulk solution under the corresponding conditions. The larger the size of the well, the lower the yield became. Selective formation of asymmetric tertiary complex was also successful. Treatment of a SA tetramer captured in a well with a biotinylated, long dsDNA has shown that the captured SA still preserves its binding ability to additional biotinylated target.

DOI： 10.1021/bc900426p

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Stepwise introduction of multiple streptavidin tetramers into a nanoarray formed in a stick-like punched DNA origami as well as selective removal of predetermined tetramer from the array were successfully achieved by applying a programmed strand displacement technique to a DNA origami scaffold.

DOI： 10.1039/c0cc00044b

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Authorship：Lead author,　Corresponding author   Language：English   Publisher：ROYAL SOC CHEMISTRY  

DNA origami is the process in which long single-stranded DNA molecules are folded into arbitrary planar nanostructures with the aid of many short staple strands. Since its initial introduction in 2006, DNA origami has dramatically widened the scope of applications of DNA nanotechnology based on the programmed assembly of branched DNA junctions. DNA origami can be used to construct not only arbitrary two-dimensional nanostructures but also nano-sized breadboards for the arraying of nanomaterials or even complicated three-dimensional nano-objects. In this review, we briefly look through the basic designs and applications of DNA origami and discuss the future of this technique.

DOI： 10.1039/b9nr00246d

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

DOI： 10.1002/asia.201000289

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

We demonstrate that intermolecular stacking is capable of forming one-dimensional arrays of a blunt-ended 3-helix DNA motif. The array can be visualized in the atomic force microscopy through conjugated streptavidin nanoparticles. We estimate the strength of the triple stacking interaction to be -8.6 kcal mol(-1).

DOI： 10.1039/c0cc01167c

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

A new caged thymidine, 3-N-(2-(2-nitrophenyl)propyloxymethyl)thymidine (T(NPPOM)) was synthesized and used as a site-selective terminator of DNA-polymerase reaction in light-assisted cohesive-ending PCR (LACE-PCR), which directly gives sticky-ended PCR products after brief UVA irradiation. Primer-extension experiments using a template involving T(NPPOM) have shown that this caged inucleotide efficiently and site-selectively blocks reactions of a variety of polymerases commonly used in PCR Misincorporation of nucleobases, observed with the use of other previously reported caged thymidines, scarcely occurred. It has turned out that a slight structural difference of caging groups can significantly improve the termination yield of polymerase reactions. A LACE-PCR product coding GFP gene was prepared by using primers containing T(NPPOM) and was ligated with a vector fragment prepared using restriction enzymes. The resulting recombinant vector successfully transformed E. coli.

DOI： 10.1021/bc900254e

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Authorship：Lead author,　Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Two types of 5&apos;-beta-CyD-DNA conjugates were synthesized using two different strategies and were hybridized with cDNA conjugates bearing various possible guest compounds at the 3&apos; ends. One of the beta-CyD conjugates was synthesized on the basis of solid-phase postmodification of DNA with a monoamino-beta-CyD derivative on a synthesis column for automated DNA synthesis. The other beta-CyD conjugate was synthesized by the solution-phase coupling of DNA with a monomercapto-beta-CyD derivative using a heterobifunctional cross-coupling reagent. When these 5&apos;-beta-CyD-DNA conjugates were hybridized with cDNA conjugates bearing 1-adamantancacetic acid at the 3&apos; ends, significant stabilization of the duplexes was observed as compared with the control duplex without beta-CyD. Duplexes of 5&apos;-beta-CyD-DNA conjugates and complementary 3&apos;-dansyl-glycine-DNA conjugates were also moderately stabilized. Thermodynamic measurements revealed that. the host-guest inclusion interactions between beta-CyD and 1-adamantaneacetic acid or dansyl-glycine are roughly as strong as those found in bulk solution even if they are tethered to the ends of the DNA.

DOI： 10.1021/bc900200c

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

A new punched DNA origami assembly with periodic nanometer-scale wells has been successfully designed and constructed. Through the attachment of two biotins at the two edges of each well, just one streptavidin (SA) tetramer (d=5 nm) was size-selectively captured in each 6.8 x 12 x 2.0 nm well; this allowed formation of a 28 nm-period SA nanoarray of individual molecules. The position of SA capture can be fully controlled by placement of biotins in the nanoarray well. Moreover, construction of a 2D nanoarray of individual SA tetramers through selective positioning of SA tetramers in any desired wells in a complex of such punched origami motifs is also possible. The stability of the SA captured by this fixation strategy (DNA wells and two biotin linkers) was directly compared on the same molecule with the stability of SA captured with other possible strategies that do not employ wells or two linkers. In this way, the robustness of this means of fixation was clearly established.

DOI： 10.1002/cbic.200900229

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

Two kinds of new acridine-DNA conjugates were synthesized by attaching acridines with bulky substituents to the end of DNA. These conjugates were hybridized to complementary RNA in combination with another unmodified DNA that hybridize to the adjacent fraction of the RNA, and were used as site-selective RNA activators for site-selective RNA cleavage catalyzed by Lu-III. The site-selective hydrolyses by these combinations are several times as fast as that achieved with the use of commercially available acridine moiety.

DOI： 10.1246/cl.2009.432

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

A box-shaped 3D-DNA origami has been successfully constructed by selective closing of a preformed open motif, and identified by atomic force microscopy and dynamic light scattering analysis.

DOI： 10.1039/b907800b

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Publishing type：Research paper (international conference proceedings)  

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

A hybrid molecule of cyclodextrin (CyD) and DNA, two major subjects in supramolecular chemistry, should open a new research field in nanoscience. By capping the end of a pseudorotaxane, formed between alpha-CyD and dodecylamine-modified DNA, with 1-adamantaneacetic acid, a DNA/alpha-CyD-rotaxane conjugate has been successfully synthesized and characterized.

DOI： 10.1246/cl.2008.996

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

In order to terminate the polymerase reaction at a desired position, a caged thymine derivative-4-O-[2-(2-nitrophenyl)propyl]thymine-was incorporated into PCR primers. In the PCR cycles, the elongation of the nascent strand (5'-&gt; 3' direction) by polymerase was site-selectively terminated at the 3'-side of T-NPP Accordingly, predetermined protruding ends were obtained after the removal of the protecting group by short UVA irradiation. Recombinant vectors coding the GFP gene were successfully prepared by direct ligation of these light-assisted cohesive-ending PCR (LACE-PCR) products with scission fragments obtained by use either of restriction enzymes or of artificial restriction DNA cutters and were used for transformation of E. coli.

DOI： 10.1002/cbic.200800285

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

We describe the synthesis of a hybrid DNA/organic macrocycle that is prepared by formation of an amide linkage across one full turn of DNA. Formation of a catenane proved that the linkage crossed a turn rather than running along the phosphodiester backbone contour. The product, a doubly tailed catenane, contains 5&apos;- and 3&apos;-termini that can be functionalized further or used to incorporate the catenane structure into other DNA assemblies.

DOI： 10.1021/ja8041096

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Authorship：Corresponding author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

A caged DNA template, which bears a caged thymine [4-O[2-(2-nitrophenyl)propyl]thymine, T-NPP} near its 5'-end, was prepared, and used for in vitro DNA replication. The photo labile 2-(2-nitrophenyl)propyl (NPP) group efficiently blocked DNA polymerase reaction, and site-selectively terminated the extension of complementary strand there. This NPP-group can be removed by simple 30-min UVA irradiation to the solution, to give restriction-enzyme-free sticky end on the template strand.

DOI： 10.1246/cl.2008.584

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

DOI： 10.1002/anie.200800028

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Publishing type：Research paper (international conference proceedings)  

DOI： 10.1093/nass/nrn237

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PubMed

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：TAYLOR & FRANCIS INC  

Photo-responsive phosphoramidite monomers, which bear an azobenzene between acridine and the phosphoramidite unit, were synthesized, and incorporated into oligonucleotides. Upon UV irradiation, the azobenzene in the modified DNA efficiently isomerized from the trans isomer into the cis isomer. Although the T(m) values of their duplexes with complementary DNA were not much changed by the isomerization, site-selective RNA scission was significantly accelerated by the UV irradiation when Mn(II) ion was used as the catalyst for RNA scission.

DOI： 10.1080/15257770802400099

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BENTHAM SCIENCE PUBL LTD  

Recent developments in artificial enzymes for site-selective scission of RNA have been reviewed, and their advantages over ribozymes are discussed. Most of previous reports involve covalent fixation of molecular scissors to sequence-recognizing moieties. However, non-covalent strategy, in which these two components are never covalently bound each other, has made remarkable progresses. When oligonucleotide bearing an acridine (site-selective activator) forms duplex with RNA substrate, the phosphodiester linkage of the RNA in front of the acridine is selectively activated and hydrolyzed by various metal ions (e.g., Lu(III). These non-covalent artificial ribonucleases are simple enough to be used for various more complicated systems. For example, tandem activator for clipping of desired fragment from long RNA substrate is obtained by attaching two acridines to an oligonucleotide. By analyzing the resultant RNA fragment with MALDI-TOFMS, the RNA substrate is accurately genotyped in terms of both single nucleotide polymorphisms (SNPs) and insertion/deletion polymorphisms (Indels).

DOI： 10.2174/138527207782418717

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

DNA nanotubes are cylinder-like structures formed from DNA double-helical molecules whose helix axes are fused at least twice by crossovers. It is potentially useful to use such tubes as sheaths around rodlike species that arise in biological systems and in nanotechnology. It seems easiest to obtain such sheathing by joining two or more components around an object rather than attempting to thread the object through a cavity in the tube. We report two examples of tubes containing a specific number of helices that are assembled from half-tube components. These tubes are a six-helix bundle and an eight-helix bundle, constructed respectively from two bent triple-crossover (BTX) molecules and from two four-helix arched motifs. Both species contain single strands in one molecule that are missing in its mate. The six-helix bundle is formed from two different BTX molecules, whereas the eight-helix species is a closed cyclic dimer of the same molecule. We demonstrate the formation of these species by gel electrophoresis, and we examine their arrangement into long one-dimensional arrays by means of atomic force microscopy.

DOI： 10.1021/nl070828k

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Publishing type：Research paper (international conference proceedings)  

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE SA  

Novel systems for site-selective RNA scission are prepared by combining lanthanide(III) ions with oligonucleotides bearing an acridine. The modified oligonucleotide forms a heteroduplex with the substrate RNA, and selectively activates the phosphodiester linkages in front of the acridine. As a result, these linkages are preferentially hydrolyzed over the others, even though the lanthanide(III) ions are not fixed anywhere. The scission is efficient under physiological conditions, irrespective of the sequence at the target site. Effect of the kind of the lanthanide on the scission is emphasized. (c) 2005 Elsevier B.V. All rights reserved.

DOI： 10.1016/j.jallcom.2004.12.149

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：ELSEVIER SCIENCE INC  

Nucleotide insertion/deletion polymorphisms (indels) in ApoE gene were precisely genotyped using artificial ribonucleases and MALDI-TOF MS. The RNA fragments for MS analysis were prepared by treating RNA specimens with our artificial ribonucleases, which consist of LuCl3 (molecular scissors) and oligonucleotides bearing two acridine groups (RNA-activator for site-selective scission). RNA scission by Lu(III) ion always occurred at the phosphodiester linkages in front of the two acridines, even when the RNA specimens involved consecutive cytidine sequences of different lengths. Thus, even complicated mixtures of these indel specimens were completely genotyped by using only one acridine-bearing oligonucleotide and by subjecting the reaction mixture to single MS measurement. Moreover, single nucleotide polymorphism (SNP) in the consecutive sequences could be genotyped simultaneously with the indels.

DOI： 10.1016/j.jasms.2005.083.016

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：SPRINGER  

Iminodiacetate DNA conjugates and acridine-DNA conjugates were synthesized and combined for site-selective RNA hydrolysis by Lu(III). When these conjugates form a ternary complex with complementary RNA, the Lu(III)-iminodiacetate complex is placed near the target phosphodiester linkage of RNA which is in front of the acridine and is activated by noncovalent interactions. The site-selective hydrolysis by these combinations is several times as fast as that achieved by combining unmodified DNA (without iminodiacetate) and the acridine-DNA conjugate.

DOI： 10.1007/s00775-005-0638-4

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Chirally pure phosphoramidite monomers bearing 9-amino-6-chloro-2-methoxyacridine were synthesized from D- or L-threoninol and omega-aminocarboxylic acid, and incorporated into oligonucleotides. These acridine-DNA conjugates formed stable duplexes with complementary RNA because of intercalation of the acridine to DNA/RNA heteroduplexes. The stability of duplexes was not very dependent on either the chirality of the central carbon bearing the acridine or the length of the side chain. However, the ability for site-selective activation of the phosphodiester linkage in front of the acridine, which induced Lu(III)-promoted RNA scission, was strongly dependent on these two factors. The largest activation was achieved when the monomer unit was prepared from L-threoninol and 4-aminobutyric acid and the acridine was bound to the amino group. By attaching the more acidic 9-amino-2-methoxy-6-nitroacridine to this optimized scaffold, a quite effective acridine-DNA conjugate for site-selective RNA scission was obtained.

DOI： 10.1021/bc049698m

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

When a one-base gap was formed in substrate RNA by using two oligonucleotides, the phosphodiester linkage at the gap-site was activated and selectively hydrolyzed by ethylenediamine. This site-selective hydrolysis was further promoted by connecting two gap-forming oligonucleotides with 1,3-propanediol linker.

DOI： 10.1246/cl.2004.1012

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：PERGAMON-ELSEVIER SCIENCE LTD  

Through a series of linkers, 9-amino-2-methoxy-6-nitroacridine and 9-amino-6-chloro-2-methoxyacridine were tethered to the middle of oligonucleotide, and the abilities of these conjugates for site-selective activation of RNA (inducing site-selective scission by Lu(III)) were compared. The RNA-activating ability was strongly dependent on the structures of both acridine and linker. By tethering 9-amino-2-methoxy-6-nitroacridine with a rigid and chiral linker, derived front L-threoninol, quite fast site-selective RNA scission was accomplished. (C) 2004 Published by Elsevier Ltd.

DOI： 10.1016/j.tetlet.2004.03.102

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Artificial enzymes for selective scission of RNA at two designated sites, which are valuable for advanced RNA science, have been prepared by combining lanthanide(III) ion with an oligonucleotide bearing two acridine groups. When these modified oligonucleotides form heteroduplexes with substrate RNA, the two phosphodiester linkages in front of the acridines are selectively activated and preferentially hydrolyzed by lanthanide ion. This two-site RNA scission does not require any specific RNA sequence at the scission sites, and the length of clipped RNA fragment is easily and precisely controllable by changing the distance between two acridine groups in the modified oligonucleotide. The two-site scission is also successful even when the substrate RNA has higher-order structures. By using these two-site RNA cutters, RNA fragments of predetermined length were obtained from long RNA substrates and analyzed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Single nucleotide polymorphisms in homozygous and heterozygous samples were accurately and easily detected in terms of the difference in mass number. Multiplex analyses of in vitro transcripts from human genome were also successful.

DOI： 10.1021/ja0389568

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：BENTHAM SCIENCE PUBL LTD  

Two new approaches for SNP genotyping are described. The one is based on tandem site-selective RNA scission and the genotype is determined by MALDI-TOF/MS analyses of clipped short RNA. The other is visual SNP genotyping with combinations of peptide nucleic acid (PNA) and single-stranded DNA specific nucleases.

DOI： 10.2174/1570193043488999

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Publishing type：Research paper (international conference proceedings)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

Two phosphoramidite monomers bearing acridine, which differ in the configuration at the branching point of the linker, have been synthesized and incorporated in DNA. In site-selective RNA scission by Lu(III), the DNA derived from L-threoninol linker is 2.5 times as effective as that from D-threoninol, confirming the importance of appropriate stereochemistry for efficient RNA activation.

DOI： 10.1246/cl.2003.464

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

Short RNA fragments containing single nucleotide polymorphism (SNP) sites have been selectively clipped out of substrate RNA by using complementary DNA having two acridine residues and Lu-III, and the genotype of the substrate is accurately and easily determined by mass analysis of these fragments.

DOI： 10.1039/b300368j

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Publishing type：Research paper (international conference proceedings)  

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

New types of RNA cutters for site-selective scission are prepared by combining metal ions with oligonucleotides bearing an acridine. Both lanthanide(M) ions and various divalent metal ions (e.g., Zn(H), Mn(H), and Mg(H)) are used without being bound to any sequence-recognizing moiety. The modified oligonucleotide forms a hetero-duplex with the RNA, and activates the phosphodiester linkages in front of the acridine. As a result, these linkages are preferentially hydrolyzed over the others, even though the metal ions are not fixed anywhere. The scission is efficient under physiological conditions, irrespective of the sequence at the target site. Site-selective RNA scission is also accomplished by combining an oligonucleotide bearing an acridine at its terminus, another unmodified oligonucleotide, and a metal ion. In the proposed mechanism, the acridine pushes the unpaired ribonucleotide out of the hetero-duplex and changes the conformation of RNA at the target site for the sequence-selective activation.

DOI： 10.1246/bcsj.75.2547

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

9-Amino-2-methoxy-6-nitroacridine (1a) is conjugated with oligonucleotide for site-selective RNA hydrolysis. When this conjugate forms a duplex with complementary RNA, the phosphodiester linkage of the RNA in front of 1a is activated and selectively hydrolyzed by Lu(III) ion. Covalent fixation of the metal ion to sequence-recognizing moiety is unnecessary. The site-selective hydrolysis by this conjugate is 2.2 times as fast as that by the oligonucleotide bearing 9-amino-6-chloro-2-methoxyacridine (1b), which hitherto has been the most active for the RNA activation. The acridine derivative 1a is more acidic than 1b, and thus is more effective as acid catalyst for the RNA hydrolysis. © 2002 Elsevier Science Ltd. All rights reserved.

DOI： 10.1016/S0040-4039(02)02017-8

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Three types of DNA conjugates having 9-acridinecarboxamide, 9-aminoacridine, and 9-amino-6-chloro-2-methoxyacridine at the 5'-ends were synthesized and used for site-selective RNA scission together with another unmodified DNA and Lu(III) ion. The target phosphodiester linkages in the substrate RNA were selectively and efficiently activated and were hydrolyzed by free Lu(III) ion. The conjugate bearing 9-amino-6-chloro-2-methoxyacridine was the most active. However, its duplex with the substrate RNA was almost as stable as that of the 9-aminoacridine-bearing conjugate, which was much less active for the RNA activation. The 9-acridinecarboxamide-bearing conjugate was only marginally active. The substituents on the acridine groups in these conjugates positively participate in the present RNA activation, probably by fixing the orientation of the acridine rings.

DOI： 10.1021/bc015573v

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Publishing type：Research paper (international conference proceedings)  

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

By using two oligonucleotides as cofactors, Mg(II) ion selectively and efficiently hydrolyzed RNA at the target site under physiological conditions. The site-selective hydrolysis was further accelerated by introducing an acridine to oligonucleotides.

DOI： 10.1246/cl.2001.584

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Language：English   Publishing type：Part of collection (book)   Publisher：Academic Press Inc.  

DOI： 10.1016/S0076-6879(01)41170-0

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PubMed

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Publishing type：Research paper (international conference proceedings)  

DOI： 10.1093/nass/1.1.131

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

Binary non-covalent systems for site-selective RNA scission are prepared from Lu(III) ion and a DNA bearing an acridine in the internal position. On the formation of DNA/RNA hetero-duplex, the target phosphodiester linkage is activated and preferentially hydrolyzed.

DOI： 10.1246/cl.2000.1378

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：ROYAL SOC CHEMISTRY  

The target phosphodiester linkage in RNA is activated by the combination of acridine-attached DNA and unmodified DNA, so that the RNA is site-selectively hydrolysed at this linkage by free Lu-III ion.

DOI： 10.1039/B006772P

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)   Publisher：CHEMICAL SOC JAPAN  

By using non-covalent combinations of Lu(III) ion and two DNA oligomers, each of which is complementary with a part of RNA, the RNA is sequence-selectively hydrolyzed. When all the ribonucleotides, except for three consecutive ones, form base-pairs with the DNA oligomers, the selective scission occurs at the 3'-side of the middle of these three non-pairing ribonucleotides.

DOI： 10.1246/cl.1999.1035

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：WILEY-V C H VERLAG GMBH  

DOI： 10.1002/(SICI)1521-3773(19981217)37:23<3284::AID-ANIE3284>3.0.CO;2-D

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Language：English   Publishing type：Research paper (scientific journal)   Publisher：AMER CHEMICAL SOC  

Phosphoramidite monomers having a benzyl or ethyl ester in the side chain have been synthesized for the facile and selective functionalization of oligonucleotides. Various amino compounds were incorporated into the desired sites in oligonucleotides by aminolysis of the esters. The conjugates, in which oligoamines (catalysts for RNA hydrolysis) were interposed between two oligonucleotides, hydrolyzed RNA substrates at exactly the target sites, which was consistent with the results of a computer-modeling study.

DOI： 10.1021/jo9611780

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Publishing type：Research paper (international conference proceedings)  

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Total pages：xvi, 478p   Language：Japanese  

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Language：Japanese   Publisher：日本バイオマテリアル学会  

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Language：Japanese   Publisher：日本DDS学会  

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Language：Japanese   Publisher：日本バイオマテリアル学会  

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Language：Japanese   Publisher：日本DDS学会  

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Language：Japanese   Publisher：関西大学先端科学技術推進機構  

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Language：Japanese   Publisher：関西大学先端科学技術推進機構  

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Language：Japanese   Publisher：関西大学先端科学技術推進機構  

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Language：Japanese   Publisher：関西大学先端科学技術推進機構  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER CHEMICAL SOC  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER CHEMICAL SOC  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER CHEMICAL SOC  

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Language：English   Publishing type：Research paper, summary (international conference)   Publisher：AMER CHEMICAL SOC  

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Event date： 2024.3

Presentation type：Poster presentation  

Venue：東京大学  

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Event date： 2023.11

Presentation type：Poster presentation  

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Event date： 2023.10

Presentation type：Oral presentation (general)  

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Event date： 2023.10

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Event date： 2023.10

Presentation type：Poster presentation  

Venue：タワーホール船堀  

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Event date： 2023.9

Presentation type：Oral presentation (general)  

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Event date： 2023.9

Presentation type：Oral presentation (general)  

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Event date： 2023.9

Presentation type：Poster presentation  

Venue：東北大学  

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Event date： 2023.9

Presentation type：Oral presentation (general)  

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Event date： 2023.9

Presentation type：Oral presentation (invited, special)  

Venue：Hangzhou   Country：China  

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Event date： 2020.11

Venue：オンライン開催  

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Venue：オンライン  

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Venue：Online  

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Venue：Online  

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Venue：東京理科大学  

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Venue：東京理科大学  

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Event date： 2020.3

Venue：東京理科大学  

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Event date： 2020.1

Venue：Chiba University  

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Event date： 2019.11

Venue：Yokohama Media and Communications Center  

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Event date： 2019.11

Venue：Yokohama Media and Communications Center  

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Venue：つくば国際会議場  

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Venue：つくば国際会議場  

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Venue：タワーホール船堀  

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Event date： 2019.9

Venue：福井大学  

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Event date： 2019.9

Venue：福井大学  

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Event date： 2019.9

Venue：福井大学  

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Event date： 2019.9

Venue：板橋区立文化会館小ホール  

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Event date： 2019.9

Venue：国立循環器病センター  

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Event date： 2019.9

Venue：国立循環器病センター  

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Event date： 2019.9

Venue：Tohoku University  

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Event date： 2019.9

Venue：Tohoku University  

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Event date： 2019.9

Venue：Tohoku University  

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Event date： 2019.9

Venue：Tohoku University  

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Venue：Tohoku University  

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Event date： 2019.8

Venue：Chulalongkorn University, Bangkok (Thailand)  

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Event date： 2019.8

Venue：Chulalongkorn University, Bangkok (Thailand)  

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Event date： 2019.8

Venue：Chulalongkorn University, Bangkok (Thailand)  

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Event date： 2019.8

Venue：Chulalongkorn University, Bangkok (Thailand)  

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Event date： 2019.7

Venue：Konan University  

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Event date： 2019.7

Venue：ホテル阪急エキスポパーク（大阪）  

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Event date： 2019.7

Venue：ホテル阪急エキスポパーク（大阪）  

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Venue：Snowbird, UT (USA)  

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Event date： 2019.3

Venue：甲南大学  

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Event date： 2019.3

Venue：甲南大学  

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Venue：東京工業大学  

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Venue：東京工業大学  

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Venue：東京工業大学  

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Venue：タワーホール船堀  

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Venue：タワーホール船堀  

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Venue：タワーホール船堀  

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Venue：タワーホール船堀  

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Venue：タワーホール船堀  

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