Author: Richter Sara Gatto Barbara Fabris Daniele
Publisher: Oxford University Press
ISSN: 1362-4962
Source: Nucleic Acids Research, Vol.31, Iss.17, 2003-09, pp. : 5149-5156
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Abstract
Clerocidin (CL) is an effective topoisomerase II‐poison, which has been shown to produce DNA depurination and strand breaks per se at the guanine (G) level. To elucidate the roles played by the different functional groups of CL in the reactivity towards nucleic acids, we investigated CL derivatives with key structural modifications. The derivatives were reacted with plasmid, single‐/double‐stranded DNA and isolated 2′‐deoxy‐guanosines (dG). We show here that an intact oxirane ring is essential to achieve DNA modification and depurination. Through HPLC/MS and MS/MS techniques we were able to unambiguously characterize adducts obtained by reacting isolated dG and single‐/double‐stranded DNA with the drugs, indicating beyond reasonable doubt that the structure of a typical adduct is formed by epoxide alkylation at N
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