PMID: 11330470May 2, 2001Paper

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

Journal of Inorganic Biochemistry
N J WheateJ G Collins

Abstract

The non-covalent binding of [(en)Pt(mu-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(mu-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(mu-dpzm)2Pt(en)]4+ was sufficiently stab...Continue Reading

References

Nov 1, 1992·Journal of Biomolecular NMR·M PiottoV Sklenár
Jun 1, 1997·European Journal of Biochemistry·R ZaludováV Brabec
May 29, 2000·Chemico-biological Interactions·L R FergusonD R Phillips
Jun 17, 2000·Journal of Inorganic Biochemistry·N J Wheate, J G Collins

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Citations

Aug 26, 2010·Nucleic Acids Research·Seiji KomedaLoren Dean Williams
Nov 8, 2006·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Alexandra MyariViktor Brabec
Jul 27, 2007·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Sharon KempJanice R Aldrich-Wright
Oct 2, 2004·Journal of Inorganic Biochemistry·J Grant Collins, Nial J Wheate
Jun 14, 2012·Inorganic Chemistry·Yulia Yu Scaffidi-DomianelloBernhard K Keppler

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