2004年7月
Enantioselective DNA alkylation by a pyrrole-imidazole S-CIB conjugate
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
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- 巻
- 126
- 号
- 29
- 開始ページ
- 8948
- 終了ページ
- 8955
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.1021/ja049398f
- 出版者・発行元
- AMER CHEMICAL SOC
Conjugates 12S and 12R of N-methylpyrrole (Py)-N-methylimidazole (Im) seven-ringed hairpin polyamide with both enantiomers of 1,2,9,9a-tetrahylrocyclopropa[1,2-c]benz[1,2-e]indol-4-one (CBI) were synthesized, and their DNA alkylating activity was examined. High-resolution denaturing gel electrophoresis revealed that 12S selectively and efficiently alkylated at one match sequence, 5'-TGACCA-3', in 450-by DNA fragments. The selectivity and efficiency of the DNA alkylation by 12S were higher than those of the corresponding cyclopropapyrroloindole (CPI) conjugate, 11. In sharp contrast, another enantiomer, 12R, showed very weak DNA alkylating activity. Product analysis of the synthetic decanucleotide confirmed that the alkylating activity of 12S was comparable with 11 and that 12S had a significantly higher reactivity than 12R. The enantioselective reactivity of 12S and 12R is assumed to be due to the location of the alkylating cyclopropane ring of the CBI unit in the minor groove of the DNA duplex. Since the CBI unit can be synthesized from commercially available 1,3-naphthalenediol, the present results open up the possibility of large-scale synthesis of alkylating Py-Im polyamides for facilitating their use in future animal studies.
- リンク情報
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- DOI
- https://doi.org/10.1021/ja049398f
- J-GLOBAL
- https://jglobal.jst.go.jp/detail?JGLOBAL_ID=200902278964893470
- PubMed
- https://www.ncbi.nlm.nih.gov/pubmed/15264825
- Web of Science
- https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000222855300032&DestApp=WOS_CPL
- ID情報
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- DOI : 10.1021/ja049398f
- ISSN : 0002-7863
- J-Global ID : 200902278964893470
- PubMed ID : 15264825
- Web of Science ID : WOS:000222855300032