Biophysical studies of the modification of poly(rG) . poly(rC) by cisplatin. Relations to the biological activity of the complex

Chem Biol Interact. 1991;78(1):1-12. doi: 10.1016/0009-2797(91)90098-r.

Abstract

The integrity of the double-stranded complex polyriboguanylic.polyribocytidylic acid [poly(rG).poly(rC)] modified by antitumour cis-diamminedichloroplatinum(II)(cis-DDP) was studied with the aid of differential pulse polarography and terbium fluorescence measurement. The modification was made to level corresponding to rb = 0.05 (rb is defined as the number of platinum atoms covalently bound per one nucleotide residue). Two modes of the modification of the polynucleotide complex were employed: The action of cis-DDP on poly(G) before formation of the complex with poly(C) and on the complex already formed from non-modified polynucleotides. It was shown that in the latter case modification disordered the integrity of the complex only negligibly. while in the former case the modification resulted in a noticeably more extensive disturbance of the double-stranded polynucleotide complex. Moreover, the modification of the complex (after its formation) at rb = 0.02 led to improved interferon-inducing and antiviral activity of poly(rG).poly(rC) tested on mice infected by influenza virus. It was suggested that the combined effects of interferon-inducing and antiviral activities of poly(rG).poly(rC) and antiviral activity of cis-DDP may result in an increased effect over and above what may be expected from the actions of the two modalities separately.

MeSH terms

  • Antiviral Agents / metabolism
  • Chromatography, Gel / methods
  • Cisplatin / pharmacology*
  • Fluorescence
  • Interferon Inducers
  • Molecular Weight
  • Polarography / methods
  • Poly C / chemistry
  • Poly C / metabolism*
  • Poly G / chemistry
  • Poly G / metabolism*
  • Terbium / metabolism

Substances

  • Antiviral Agents
  • Interferon Inducers
  • Terbium
  • Poly G
  • poly G-poly C
  • Poly C
  • Cisplatin