title: The leaving group strongly affects H₂O₂-induced DNA cross-linking by arylboronates.
abstract: We evaluated the effects of the benzylic leaving group and core structure of arylboronates on H2O2-induced formation of bisquinone methides for DNA interstrand cross-linking. The mechanism of DNA cross-linking induced by these arylboronates involves generation of phenol intermediates followed by departure of benzylic leaving groups leading to QMs which directly cross-link DNA via alkylation. The QM formation is the rate-determining step for DNA cross-linking. A better leaving group (Br) and stepwise bisquinone methide formation increased interstrand cross-linking efficiency. These findings provide essential guidelines for designing novel anticancer prodrugs.
authors.affiliation: Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee , 3210 North Cramer Street, Milwaukee, Wisconsin 53211, United States.
authors.forename: Sheng
authors.initials: S
authors.lastname: Cao
authors.forename: Yibin
authors.initials: Y
authors.lastname: Wang
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Peng
mesh_terms: D001897:Boronic Acids / Q000737:chemistry*; D003432:Cross-Linking Reagents / Q000737:chemistry*; D018360:Crystallography, X-Ray; D004247:DNA / Q000737:chemistry*; D006861:Hydrogen Peroxide / Q000737:chemistry*; D008958:Models, Molecular; D015394:Molecular Structure
chemical_list: D001897:Boronic Acids; D003432:Cross-Linking Reagents; D004247:DNA; D006861:Hydrogen Peroxide