Studies on the mechanism of action of azinomycin B: Definition of regioselectivity and sequence selectivity of DNA cross-link formation and clarification of the role of the naphthoate

被引：67

作者：

Coleman, RS ^{[1
]}

Perez, RJ ^{[1
]}

Burk, CH ^{[1
]}

Navarro, A ^{[1
]}

机构：

[1] Ohio State Univ, Dept Chem, Columbus, OH 43210 USA

来源：

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY | 2002年 / 124卷 / 44期

关键词：

D O I：

10.1021/ja025563k

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

Evaluation of the sequence selectivity, noncovalent association, and orientation of the DNA cross-linking agent azinomycin B on its duplex DNA receptor is described. A strong correlation between sequence nucleophilicity and cross-linking yield was observed, and steric effects due to the thymine C5-methyl group were identified. Detailed studies on the role of the azinomycin naphthoate using viscometry, fluorescence contact energy transfer, and DNA unwinding assays point to a nonintercalative binding mode for this group. A kinetic assay for agent regioselectivity was used to determine the orientation of binding and covalent cross-link formation.

引用

页码：13008 / 13017

页数：10

共 38 条

[1] DNA cross-linking by azinomycin B: Monte Carlo simulations in the evaluation of sequence selectivity [J].