A H-1 NMR study of the oligonucleotide binding of [(en)Pt(mu-dpzm)(2)Pt(en)]Cl-4

The non-covalent binding of [(en)Pt(mu-dpzm)(2)Pt(en)](4+) to the dodecanuc leotides d(CGCGAATTCGCG)(2) and d(CAATCCGGATTG)(2)has been studied by H-1 N MR spectroscopy in order to gain a greater understanding of the pre-covalen t binding association of cationic dinuclear platinum(II) anti-cancer drugs. NOESY experiments showed that the metal complex bound in the minor groove at the A/T rich regions of both dodecanucleotides. The metal complex did no t induce any major DNA conformational changes. However, given the relative dimensions of the DNA minor groove and the metal complex, it is reasonable to expect that the metal complex binding significantly widens the minor gro ove at the A/T rich binding sites. The results of this study suggest that a lthough dinuclear platinum(II) anti-cancer drugs covalently bind at GC sequ ences in the DNA major groove, they will preferentially associate with AT s equences in the minor groove before the covalent binding. (C) 2000 Elsevier Science Inc. All rights reserved.