Effects of monofunctional platinum binding on the thermal stability and conformation of a self-complementary 22-mer

J Inorg Biochem. 2000 Oct 1;81(4):313-23. doi: 10.1016/s0162-0134(00)00120-3.

Abstract

We investigated the effect of various monofunctional platinum complexes on the thermal stability and conformation of a self-complementary 22-mer duplex oligonucleotide by means of CD and UV melting profiles. We studied several families of triamine complexes of the general formula PtA2AmCl where A2=(NH3)2 and ethylenediamine and where Am=N1-4-methyl-pyridine, N7-guanosine, and 9-ethyl-guanine. Platination by the N1-4-methyl-pyridine and 9-ethyl-guanine complexes led to a decrease in the Tm of the oligonucleotide by 2-11.5 degrees C while platination with the N7-guanosine complexes led to a rise in the melting temperature of the oligonucleotides by 4.5 degrees C. A similar inverse correlation between the two groups of platinum compounds was found in the CD spectra. In all cases, the cis isomer had a more pronounced effect on both the melting curve and the CD spectrum. The cis isomer was found to have a more destabilizing effect than its trans counterpart. This indicates that the cis geometry in fact forces a greater structural constraint on the backbone of the double helix. We have also found that the sugar of the guanosine has a significant influence on both the Tm and CD spectra; the sugar moiety contributes to the stability of the double helix, probably through the formation of hydrogen bonds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / metabolism
  • Circular Dichroism
  • DNA Adducts / chemistry
  • Nucleic Acid Conformation
  • Oligonucleotides / chemistry*
  • Oligonucleotides / metabolism*
  • Platinum Compounds / chemistry*
  • Platinum Compounds / metabolism*
  • Ultraviolet Rays

Substances

  • Antineoplastic Agents
  • DNA Adducts
  • Oligonucleotides
  • Platinum Compounds