You have full text access to this OnlineOpen article

Monofunctional platinum amine complexes destabilize DNA significantly

  1. Cornelia Bauer1,
  2. Tal Peleg-Shulman3,
  3. Dan Gibson3,4,
  4. Andrew H.-J. Wang1,2

Article first published online: 25 DEC 2001

DOI: 10.1046/j.1432-1327.1998.2560253.x

Issue

European Journal of Biochemistry

European Journal of Biochemistry

Volume 256, Issue 2, pages 253–260, September (I) 1998

Additional Information

How to Cite

Bauer, C., Peleg-Shulman, T., Gibson, D. and Wang, A. H.-J. (1998), Monofunctional platinum amine complexes destabilize DNA significantly. European Journal of Biochemistry, 256: 253–260. doi: 10.1046/j.1432-1327.1998.2560253.x

Author Information

  1. 1

    Department of Chemistry, University of Illinois at Urbana-Champaign, USA

  2. 2

    Department of Cell and Structural Biology, University of Illinois at Urbana-Champaign, USA

  3. 3

    Department of Pharmaceutical Chemistry, School of Pharmacy, Hebrew University of Jerusalem, Israel

  4. 4

    David R. Bloom, Center for Pharmacy at the Hebrew University, Israel

Publication History

  1. Issue published online: 25 DEC 2001
  2. Article first published online: 25 DEC 2001
  3. (Received 19 May 1998)

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

Get PDF (705K)

Keywords:

  • anti-cancer;
  • DNA;
  • cisplatin;
  • NMR;
  • methylpyridine.

Both cis-[Pt(NH3)2(4-Me-Py)Cl]+ and trans-[Pt(NH3)2(4-Me-Py)Cl]+ bind DNA covalently at the N7 site of guanine residues forming mono-dentate adducts. However, like cisplatin and transplatin, only the cis isomer has anti-cancer activity, whereas the trans-isomer does not. In order to understand the molecular basis of the different activities associated with cis-[Pt(NH3)2(4-Me-Py)Cl]+ and trans-[Pt(NH3)2(4-Me-Py)Cl]+, the interactions of these two platinum compounds with the DNA heptamer CCTG*TCC :GGACAGG duplex (G* is the platinated guanine) have been examined. The reaction rate of cis-[Pt(NH3)2(4-Me-Py)Cl]+ with the single-stranded CCTGTCC is significantly faster than that of the trans isomer. The solution structure of the platinum−DNA adducts has been studied by two-dimensional NMR spectroscopy. Both the cis-platinum adducts and the trans-platinum adducts destabilize the DNA duplex significantly. The melting temperature (Tm) of the platinated heptamer duplex is estimated to be 10 +C lower than for the unplatinated duplex by NMR. At 2 +C, the base pairs located on the 5′ side of the oligonucleotide, beyond the platinum lesion site, are disrupted. Over time, the platinum−DNA complex decomposes and the cis-[Pt(NH3)2(4-Me-Py)] platinum complex is gradually detached from DNA. No interstrand crosslinking is observed. The biological implications of the structural studies are discussed.

Get PDF (705K)