Effects of geometric isomerism and anions on the kinetics and mechanism of the stepwise formation of long-range DNA interstrand cross-links by dinuclear platinum antitumor complexes.

ABSTRACT: Reported herein is a detailed study of the kinetics and mechanism of formation of a 1,4-GG interstrand cross-link by the dinuclear platinum anticancer compound [15N][{cis-PtCl(NH3)2}2{mu-NH2(CH2)6NH2}]2+ (1,1/c,c (1)). The reaction of [15N]1 with 5'-{d(ATATGTACATAT)2} (I) has been studied by [1H,15N] HSQC NMR spectroscopy in the presence of different concentrations of phosphate. In contrast with the geometric trans isomer (1,1/t,t), there was no evidence for an electrostatic preassociation of 1,1/c,c with the polyanionic DNA surface, and the pseudo-first-order rate constant for the aquation of [(15)N]1 was actually slightly higher (rather than lower) than that in the absence of DNA. When phosphate is absent, the overall rate of formation of the cross-link is quite similar for the two geome

SUBMITTER: Zhang J 

PROVIDER: S-EPMC2825901 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature