東京大学 · 生化学・遺伝学・分子生物学
Makoto Komiyama教授の研究室は、ランタニドイオンを用いた核酸の特異的加水分解反応のメカニズム解明に加え、人工制限酵素の開発やDNAオリガミを活用したナノ構築技術の確立を柱としています。特に、DNAやRNAのサイト選択的切断を実現する化学的アプローチと、分子認識に基づく精密ナノ構造の設計が融合された「ナノアーキテクトニクス」の展開が特徴です。これにより、がん治療への応用や、標的ドラッグデリバリー、バイオセンサー開発への基盤技術が構築されています。
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A few years ago, the remarkable catalytic activity of lanthanide ions for the hydrolysis of nucleic acids was discovered. With CeIV, DNA was hydrolysed under physiological conditions. For RNA hydrolysis, the last three lanthanide ions (TmIII, YbIII, and LuIII) are superb. Furthermore, artificial restriction enzymes for site-selective scission of DNA and RNA, essential tools for the future biotechnology, have been prepared by using the lanthanide complexes. The present article emphasizes the mech
Abstract In this review, we introduce two kinds of bio-related nanoarchitectonics, DNA nanoarchitectonics and cell-macromolecular nanoarchitectonics, both of which are basically controlled by chemical strategies. The former DNA-based approach would represent the precise nature of the nanoarchitectonics based on the strict or “digital” molecular recognition between nucleic bases. This part includes functionalization of single DNAs by chemical means, modification of the main-chain or side-chain ba
Abstract Combining nanotechnology with other science disciplines is necessary to produce various materials with nanoscale structural and functional information, which is nanoarchitectonics, a novel paradigm to create useful materials. One of the basic ideas in nanoarchitectonics is use of molecular-level information to structurally design functional materials. This strategy is indeed used in some existing science fields and technical realms. For example, molecular imprinting techniques provide f
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.
This tutorial review provides recent developments in artificial cutters for site-selective scission of DNA with the focus on chemistry-based DNA cutters. They are useful tools for molecular biology and biotechnology, since their site-selectivity of scission is much higher than that of naturally occurring restriction enzymes and also their scission site is freely chosen. In order to prepare these cutters, a DNA-cutting molecule is combined with a sequence-recognizing molecule in a covalent or non
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
Totally synthetic and sequence-specific nucleases and ribonucleases, which hydrolyze DNAs and RNAs selectively at target sites, have been prepared. Lanthanide ions, which efficiently hydrolyze the phosphodiester linkages in nucleic acids, are attached to the 5'-end of synthetic DNA oligomers (sequence-recognizing sites) by use of an iminodiacetate ligand. Under physiological conditions, the hybrids selectively hydrolyze substrate DNA or RNA at the 3'-side of the sequence which is complementary w
By the combination of peptide nucleic acid (PNA) with single-stranded DNA specific nucleases, alteration of a single base to another in DNA has been detected with high accuracy. Only the DNAs in DNA/PNA duplexes involving a mismatch are efficiently hydrolyzed by these enzymes, whereas fully matching sequences are kept intact. This difference is visually scored by adding 3,3'-diethylthiadicarbocyanine, which changes its color from blue to purple upon binding to DNA/PNA duplexes. These findings ar
ADVERTISEMENT RETURN TO ISSUEPREVArticleNEXTImportance of apolar binding in complex formation of cyclodextrins with adamantanecarboxylateMakoto Komiyama and Myron L. BenderCite this: J. Am. Chem. Soc. 1978, 100, 7, 2259–2260Publication Date (Print):March 1, 1978Publication History Published online1 May 2002Published inissue 1 March 1978https://pubs.acs.org/doi/10.1021/ja00475a062https://doi.org/10.1021/ja00475a062research-articleACS PublicationsRequest reuse permissionsArticle Views210Altmetric-
Invasion of two PNA strands to double-stranded DNA is one of the most promising methods to recognize a predetermined site in double-stranded DNA (PNA = peptide nucleic acid). In order to facilitate this 'double-duplex invasion', a new type of PNA was prepared by using chiral PNA monomers in which a nucleobase was bound to the alpha-nitrogen of N-(2-aminoethyl)-d-lysine. These positively charged monomer units, introduced to defined positions in Nielsen's PNAs (poly[N-(2-aminoethyl)glycine] deriva
Even in the presence of a large excess of Zn<sup>II</sup> ions, sequence-selective RNA hydrolysis is achieved by DNA conjugates involving a dinuclear Zn<sup>II</sup> complex (shown schematically). This is because the cooperation of two Zn<sup>II</sup> ions is essential for the RNA scission.
Oligopeptides are efficiently hydrolyzed by Ce(IV) to the corresponding amino acids under mild conditions. The pseudo first-order rate constants for the hydrolysis of H-Gly-Phe-OH and H-Gly-Gly-OH at pH 7.0 and 50 degrees C are 3.5 x 10(-1) and 2.8 x 10(-1) h(-1), with [Ce(NH4)2(NO3)6]0=10mM (the half-lives are 2.0 and 2.5 h). The catalytic activity of the Ce(IV) is far greater than those of other lanthanide ions and non-lanthanide ions. No oxidative cleavage was observed under the reaction cond
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