Biophysical studies of the modification of poly(rG) . poly(rC) by cisplatin. Relations to the biological activity of the complex.
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.
Brabec
V
V
Institute of Biophysics, Czechoslovak Academy of Sciences, Brno.
Vrána
O
O
Platonova
G A
GA
Kogan
E M
EM
Sidorova
N S
NS
D000998:Antiviral Agents / Q000378:metabolism; D002850:Chromatography, Gel / Q000379:methods; D002945:Cisplatin / Q000494:pharmacology*; D005453:Fluorescence; D007369:Interferon Inducers; D008970:Molecular Weight; D011048:Polarography / Q000379:methods; D011066:Poly C / Q000737:chemistry / Q000378:metabolism*; D011068:Poly G / Q000737:chemistry / Q000378:metabolism*; D013725:Terbium / Q000378:metabolism
D000998:Antiviral Agents; D007369:Interferon Inducers; D013725:Terbium; D011068:Poly G; C008961:poly G-poly C; D011066:Poly C; D002945:Cisplatin