Kinetic analysis of the stepwise platination of single- and double-stranded GG oligonucleotides with cisplatin and cis-[PtCl(H2O)(NH 3)2]

Abstract

We report the first direct comparison of the kinetics of platination of defined single- and double-stranded DNA with the anticancer drug cisplatin. The courses of the reactions of the 14-mer duplex d(A-T-A-C-A-T-G-G-T-A-C-A-T- with [15N]cisplatin and cis-[PtCl(H2O)-(15NH 3)2]+ and of each of the single strands with [15N]cisplatin have been studied at 298 K, pH 6, by [ 1H,15N] NMR spectroscopy. As expected the reactions of cisplatin proceed via cis-[PtCl(H2O)(NH3) 2]+, and lead to two monofunctional adducts on the duplex and two on the GG single strand. In both the GG single strand and the duplex, one of the two G's is platinated faster than the other (by a factor of ca. 4). Remarkably, ring ..