Dependence of DNA sequence selectivity and cell cytotoxicity on azinomycin A and B epoxyamide stereochemistry

被引:9
作者
Coleman, Robert S.
Woodward, Robert L.
Hayes, Amy M.
Crane, Erika A.
Artese, Anna
Ortuso, Francesco
Alcaro, Stefano
机构
[1] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA
[2] Univ Catanzaro Magna Graecia, Dipartimento Sci Farmacobiol, I-88021 Catanzaro, Italy
关键词
D O I
10.1021/ol070395s
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Evaluation of the importance of C18/C19 stereochemistry of azinomycin A/B epoxyamide partial structures with respect to DNA alkylation sequence selectivity is reported using a unique assay with a DNA oligomer containing imbedded normal (5'-GGC-3'/3'-CCG-5') and inverted (5'-CGG-3'/3'-GCC-5') azinomycin consensus cross-linking sequences. Both species were found to have unique selectivity profiles and alkylate DNA in a manner distinct from azinomycin B. Computational docking experiments support altered binding modes for the enantiomers.
引用
收藏
页码:1891 / 1894
页数:4
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