The binding of [(en)Pt(μ-dpzm)2Pt(en)]4+ to G/C-rich regions of DNA

The non-covalent binding of [(en)Pt(mu -dpzm)(2)Pt(en)](4+) to segments of DNA containing only G and C bases has been studied to gain an understanding of the pre-covalent binding association of cationic polynuclear platinum(II) anti-cancer drugs at G/C sites. H-1-NMR and CD spectroscopy were used to study the binding of the metal complex to the oligonucleotide d(GC)(5) and the polynucleotide poly(dG-dC).poly(dG-dC), respectively. NOE contacts between the metal complex protons and the oligonucleotide sugar H1' protons observed in NOESY spectra indicated that the metal complex bound in the minor groove at the central C-4 to G(7) region of the oligonucleotide. This result indicates that even though cationic polynuclear platinum(II) complexes bind covalently in the major groove at GIC sites, the pre-covalent binding association is favoured in the minor groove. CD spectra indicated that the addition of the metal complex to poly(dG-dC).poly(dG-dC) induced some conformational changes, but it was not possible to conclude that [(en)Pr(mu -dpzm)(2)Pt(en)](4+) induced a B- to Z-type DNA transition. In addition, in vitro transcription assays using the lar UV5 promoter showed that the non-covalent binding of [(en)Pt(mu -dpzm)(2)Pt(en)](4+) was sufficiently stable to inhibit transcription, and at particular sites. (C) 2001 Elsevier Science B.V. All rights reserved.