title: 4-vinyl-substituted pyrimidine nucleosides exhibit the efficient and selective formation of interstrand cross-links with RNA and duplex DNA.
abstract: The formation of interstrand cross-links in nucleic acids can have a strong impact on biological function of nucleic acids; therefore, many cross-linking agents have been developed for biological applications. Despite numerous studies, there remains a need for cross-linking agents that exhibit both efficiency and selectivity. In this study, a 4-vinyl-substituted analog of thymidine (T-vinyl derivative) was designed as a new cross-linking agent, in which the vinyl group is oriented towards the Watson-Crick face to react with the amino group of an adenine base. The interstrand cross-link formed rapidly and selectively with a uridine on the RNA substrate at the site opposite to the T-vinyl derivative. A detailed analysis of cross-link formation while varying the flanking bases of the RNA substrates indicated that interstrand cross-link formation is preferential for the adenine base on the 5'-side of the opposing uridine. In the absence of a 5'-adenine, a uridine at the opposite position underwent cross-linking. The oligodeoxynucleotides probe incorporating the T-vinyl derivative efficiently formed interstrand cross-links in parallel-type triplex DNA with high selectivity for dA in the homopurine strand. The efficiency and selectivity of the T-vinyl derivative illustrate its potential use as a unique tool in biological and materials research.
authors.affiliation: Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishimoto
authors.forename: Daichi
authors.initials: D
authors.lastname: Jitsuzaki
authors.forename: Kazumitsu
authors.initials: K
authors.lastname: Onizuka
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Taniguchi
authors.forename: Fumi
authors.initials: F
authors.lastname: Nagatsugi
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sasaki
mesh_terms: D003432:Cross-Linking Reagents / Q000138:chemical synthesis / Q000737:chemistry*; D004247:DNA / Q000737:chemistry*; D009838:Oligodeoxyribonucleotides / Q000737:chemistry*; D012313:RNA / Q000737:chemistry*; D013936:Thymidine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D014529:Uridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry; D014753:Vinyl Compounds / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D003432:Cross-Linking Reagents; D009838:Oligodeoxyribonucleotides; D014753:Vinyl Compounds; C051802:triplex DNA; D012313:RNA; D004247:DNA; D013936:Thymidine; D014529:Uridine