Specific DNA structural attributes modulate platinum anticancer drug site selection and cross-link generation.

ABSTRACT: Heavy metal compounds have toxic and medicinal potential through capacity to form strong specific bonds with macromolecules, and the interaction of platinum drugs at the major groove nitrogen atom of guanine bases primarily underlies their therapeutic activity. By crystallographic analysis of transition metal-and in particular platinum compound-DNA site selectivity in the nucleosome core, we establish that steric accessibility, which is controlled by specific structural parameters of the double helix, modulates initial guanine-metal bond formation. Moreover, DNA conformational features can be linked to both similarities and distinctions in platinum drug adduct formation between the naked and nucleosomal DNA states. Notably, structures that facilitate initial platinum-guanine bond formation

SUBMITTER: Wu B 

PROVIDER: S-EPMC3185412 | biostudies-literature | 2011 Oct

REPOSITORIES: biostudies-literature