Template-dependent biosynthesis of poly(G) x poly (C) and its antiviral activity in vitro and in vivo.
Experimental conditions for poly(G) synthesis from GTP on a poly(C) template with the aid of Escherichia coli DNA-dependent RNA polymerase were investigated. The reaction product was purified without the use of RNase. On the basis of spectral data, gel permeation chromatography, affinity adsorption and electron microscopic visualization, the poly(G) x poly(C) product was assumed to possess a high degree of structural regularity. Its in vitro and in vivo antiviral activities were compared with those of traditional poly(G) x poly(C) and poly(I) x poly(C). Template-dependent poly(G) x poly(C) was similar in its in vitro activity to poly(I) x poly(C) or even surpassed it, whereas the 'traditional' poly(G) x poly(C) was only slightly active in vitro. However, 'traditional' poly(G) x poly(C) and poly(I) x poly(C) had similar activity in vivo, whereas template-dependent poly(G) x poly(C) was much less active in vivo. The role of intramolecular structural regularity in the in vitro and in vivo antiviral activity of polyribonucleotide duplexes is discussed.
Surzhik
M A
MA
Division of Molecular and Radiation Biophysics, Petersburg Nuclear Physics Institute, Russian Academy of Sciences, Gatchina, Leningrad District.
Vilner
L M
LM
Katchurin
A L
AL
Timkovskii
A L
AL
D000818:Animals; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D002642:Chick Embryo; D002846:Chromatography, Affinity; D002850:Chromatography, Gel; D012321:DNA-Directed RNA Polymerases / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D051379:Mice; D008807:Mice, Inbred BALB C; D008854:Microscopy, Electron; D009690:Nucleic Acid Conformation; D009693:Nucleic Acid Hybridization; D011066:Poly C / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011068:Poly G / Q000096:biosynthesis* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011070:Poly I-C / Q000737:chemistry / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013698:Templates, Genetic; D014721:Vesicular stomatitis Indiana virus / Q000187:drug effects*
D000998:Antiviral Agents; D011068:Poly G; C008961:poly G-poly C; D011066:Poly C; D012321:DNA-Directed RNA Polymerases; D011070:Poly I-C