Tohoku University · Biochemistry, Genetics and Molecular Biology
Professor Fumi Nagatsugi's research lab specializes in the development of novel chemical tools for sequence-specific DNA modification and gene regulation. The lab focuses on designing oligonucleotide-based systems that enable site-directed cross-linking and alkylation of DNA, particularly targeting cytosine and thymine residues with high efficiency and selectivity. Their work centers on creating functionalized oligonucleotides—such as triplex-forming oligonucleotides (TFOs) and cross-linking oligonucleotides (CFOs)—that can selectively modify DNA in duplex or genomic contexts, offering applications in gene silencing, site-directed mutagenesis, and inhibition of microRNA function. The lab’s innovative strategies often involve smart reactive moieties like vinyl-pyrimidine or abasic site-targeting probes for controlled, stimulus-responsive DNA modification.
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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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