Bifunctional binding of cisplatin to DNA: why does cisplatin form 1,2-intrastrand cross-links with ag but not with GA?

ABSTRACT: The bifunctional binding of the anticancer drug cisplatin to two adjacent nucleobases in DNA is modeled using density functional theory. Previous experimental studies revealed that cisplatin binding to adjacent guanine and adenine is sensitive to nucleobase sequence. Whereas AG 1,2-intrastrand cross-links are commonly observed, the analogous GA adducts are not known. This study focuses on understanding this directional preference by constructing a full reaction profile using quantum chemical simulation methods. Monofunctional and bifunctional cisplatin adducts were generated, and the transition states that connect them were located for the dinucleotides d(pApG) and d(pGpA), assuming that initial platination takes place at the guanine site. Our computer simulations reveal a significant kine

SUBMITTER: Mantri Y 

PROVIDER: S-EPMC2495024 | biostudies-literature | 2007 Apr

REPOSITORIES: biostudies-literature