Kinetic Analysis of the Reactions between GG-Containing Oligonucleotides and Platinum Complexes. 1. Reactions of Single-Stranded Oligonucleotides withcis-[Pt(NH3)2(H2O)2]2+and [Pt(NH3)3(H2O)]2+

Publisher Website
Google Scholar
Abstract
Using concentration measurements based on high performance liquid chromatography, we have investigated the kinetics of reaction between single-stranded oligonucleotides containing a d(GpG) sequence, i.e., d(GG), d(TGG), d(TTGG), and d(CTGGCTCA), and the platinum complexes cis-[Pt(NH3)2(H2O)2]2+ (1) and [Pt(NH3)3(H2O)]2+ (2). The rate constants for the substitution of one aqua ligand of platinum in 1 or 2 by each guanine of the oligonucleotides were individually measured, as well as, for 1, those for the subsequent conversion of the monoadducts to the diadduct. For the platination of d(GG) and d(TGG), the rate constants are similar for the 5‘- and 3‘-guanines. The longer oligonucleotides d(TTGG) and d(CTGGCTCA) are platinated slightly faster on the 5‘-G than on the 3‘-G. 2 shows a similar slight preference for the 5‘-guanine, but it reacts by a factor of 4−10 more slowly than 1. For both complexes, the platination rate constants increase with increasing oligonucleotide length. Platination of the 5‘-G by 1 is 1 order of magnitude faster on d(CTGGCTCA) than on d(GG). Concerning the chelation step giving the GG diadduct of 1, the longer the oligonucleotide, the larger is the ratio between the rates of the cyclization of the 3‘- and 5‘-monoadducts k3‘c and k5‘c: k3‘c/k5‘c equals 1.4 for d(GG) and 3.3 for d(CTGGCTCA).

This publication has 23 references indexed in Scilit: