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

The non-covalent binding of [(en)Pt(μ-dpzm)₂Pt(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. ¹H-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 C₄ to G₇ region of the oligonucleotide. This result indicates that even though cationic polynuclear platinum(II) complexes bind covalently in the major groove at G/C 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)Pt(μ-dpzm)₂Pt(en)]⁴⁺ induced a B- to Z-type DNA transition. In addition, in vitro transcription assays using the lac UV5 promoter showed that the non-covalent binding of [(en)Pt(μ-dpzm)₂Pt(en)]⁴⁺ was sufficiently stable to inhibit transcription, and at particular sites.