東北大学 · 生化学・遺伝学・分子生物学
福岡大学薬学研究院の永津木史教授らの研究室は、核酸を標的とした特異的で効率的な化学反応を創出し、がんや遺伝子疾患の治療に応用可能な新規オリゴデオキシリボ核酸技術の開発を主眼としています。特に、二本鎖DNA内でのサイトオシンやチミンへの選択的アルキル化、および自己活性化型クロスリンク反応を用いた遺伝子発現の抑制技術に注力しています。また、miRNA機能の特異的阻害や、ポリメラーゼ反応を阻害するための標的反応など、遺伝子操作や標的医薬の開発に貢献する新規化学戦略の確立を目指しています。
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ADVERTISEMENT RETURN TO ISSUEPREVCommunicationNEXTHighly Efficient and Selective Cross-Linking to Cytidine Based on a New Strategy for Auto-Activation within a DuplexFumi Nagatsugi, Takeshi Kawasaki, Daisaku Usui, Minoru Maeda, and Shigeki SasakiView Author Information Graduate School of Pharmaceutical Sciences Kyushu University, 3-1-1 Maidashi Higashi-ku, Fukuoka 812-8582, Japan Cite this: J. Am. Chem. Soc. 1999, 121, 28, 6753–6754Publication Date (Web):July 3, 1999Publication History Received5
Interstrand cross-linking (ICL) forming oligodeoxynucleotides (ODNs) have been expected to ensure the inhibition of gene expression. In this communication, we report a highly efficient and selective ICL reaction to thymine using a 4-amino-2-vinyl-6-oxopyrimidine derivative.
The specific recognition of homopurine-homo pyrimidine regions in duplex DNA by triplex-forming oligonucleotides (TFOs) provides an attractive strategy for genetic manipulation. Alkylation of nucleobases with functionalized TFOs would have the potential for site-directed mutagenesis. Recently, we demonstrated that a TFO bearing 2-amino-6-vinylpurine derivative, 1, achieves triplex-mediated reaction with high selectivity toward the cytosine of the G-C target site. In this report, we have investig
Synthetic oligonucleotides (ONs) are valuable tools that interfere with gene expression by specifically binding to target genes in a sequence-specific manner. Reactive ONs containing cross-linking agents are expected to induce efficient inhibition because they bind covalently to target genes. In recent years, researchers have reported several cross-linking reactions that target DNA induced by external stimuli. This short review highlights recently developed novel cross-linking reactions, focusin
Masking the miRNA binding site: Crosslink-forming oligonucleotide (CFO) was used for target gene-specific inhibition of microRNA (miRNA) functions. This method can interfere with specific miRNA-mRNA interactions by recognizing sequences unique to the 3'-UTR that are inherent in each mRNA.
Selective chemical reactions with DNA, such as its labelling, are very useful in many applications. In this paper, we discuss a new strategy for the selective alkylation of DNA using an oligonucleotide containing an abasic site and alkylating probes. We designed three probes consisting of 2-AVP as a reactive moiety and three kinds of binding moiety with high affinity to duplex DNA. Among these probes, Hoechst-AVP probe exhibited high selectivity and efficient reactivity to thymine bases at the s
Guanine (G)-rich sequences can form non-canonical four stranded structures known as G-quadruplexes (G4s). The G4 structure has been found in biologically significant regions of the genomic DNA, and many G4 ligands with a high specificity and affinity have been reported. In this review, we focus on the functional G4 ligands, which not only bind to the G4 structure but also have some function, especially with inducing G4 folding, chemical reactions, and alkylation by proximity. G-quadruplexes (G4s
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