Factors affecting the rate of reaction of platinum anticancer drug models with DNA and protein targets

Becca M. Sandlin and Kevin M. Williams

NMR spectroscopy has been used to observe the effects of ligand bulk and hydrogen bonding on the rates of reaction of platinum complexes, which are analogs of the anticancer drug cisplatin, with DNA and protein residues. We have studied reactions with guanosine, guanosine 5’-monophosphate (5’-GMP) and N-acetylmethionine (N-AcMet). The nonbulky platinum complex favors reaction with 5’-GMP, a representative DNA target, because of hydrogen bonding; the bulky platinum complex favors reaction with 5’-GMP because of unfavorable steric clashes in the reaction with N-AcMet. Thus, the presence of some bulk could result in an increased reactivity with the desired DNA targets.