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 |
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Authors: | Coleman Robert S Perez Ronelito J Burk Christopher H Navarro Antonio |
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Affiliation: | Department of Chemistry, The Ohio State University, 100 West 18th Avenue, Columbus, Ohio 43210-1185, USA. coleman@chemistry.ohio-state.edu |
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Abstract: | 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. |
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