Active oligonucleotides incorporating alkylating an agent as potential sequence- and base selective modifier of gene expression.
A number of cross-linking (alkylating) agents have been developed and incorporated into the oligonulceotides for sequence selective control of gene expression. Recently, potential application of such active oligonucleotides has been expanding from use for improvement of inhibition efficiency to new biotechnology that may enable chemical alteration of genetic information. These interests in active oligonucleotides have encouraged the generation of new cross-linking agents that exhibit high efficiency for application of either in vitro or in vivo. This mini review summarizes structures of alkylating agents, in particular, a new basic skeleton for cross-linking, a 2'-deoxyribose derivative of 2-amino-6-vinylpurine that has been recently developed by the author's group. The 2-amino-6-vinylpurine has been shown to form a complex with cytidine under acidic conditions, and brings the vinyl and the amino reactive groups into proximity to achieve efficient alkylation. A new strategy was designed so that the reactivity of 2-amino-6-vinylpurine can be induced from the corresponding phenylsulfoxide derivative within a duplex with the complementary strand. The validity of the new strategy has been proven by achievement of cytidine-selective cross-linking with remarkably efficiency.
Sasaki
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Kyushu University, Graduate School of Pharmaceutical Sciences, 3-1-1 Maidashi, Higashi-ku, 812-8582, Fukuoka, Japan. sasaki@chemgate.phar.kyushu-u.ac.jp
D000477:Alkylating Agents / Q000737:chemistry* / Q000494:pharmacology; D001388:Aziridines / Q000737:chemistry / Q000494:pharmacology; D003432:Cross-Linking Reagents / Q000737:chemistry* / Q000494:pharmacology; D003521:Cyclopropanes / Q000737:chemistry / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology; D009841:Oligonucleotides / Q000737:chemistry* / Q000494:pharmacology; D011687:Purines / Q000737:chemistry*; D014753:Vinyl Compounds / Q000737:chemistry*
C432203:2-amino-6-vinylpurine; D000477:Alkylating Agents; D001388:Aziridines; D003432:Cross-Linking Reagents; D003521:Cyclopropanes; D009705:Nucleosides; D009841:Oligonucleotides; D011687:Purines; D014753:Vinyl Compounds; C033132:aziridine; C030797:cyclopropane