TEMPLATE-DEPENDENT BIOSYNTHESIS OF POLY(G)CENTER-DOT-POLY(C) AND ITS ANTIVIRAL ACTIVITY IN-VITRO AND IN-VIVO

Experimental conditions for poly(G) synthesis from GTP on a poly(C) te mplate with the aid of Escherichia coil DNA-dependent RNA polymerase w ere 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 ).poly(C) product was assumed to possess a high degree of structural r egularity. Its in vitro and in vivo antiviral activities were compared with those of traditional poly(G).poly(C) and poly(I).poly(C). Templa te-dependent poly(G).poly(C) was similar in its in vitro activity to p oly(I).poly(C) or even surpassed it, whereas the 'traditional' poly(G) .poly(C) was only slightly active in vitro. However, 'traditional' pol y(G).poly(C) and poly(I).poly(C) had similar activity in vivo, whereas template-dependent poly(G).poly(C) was much less active in vivo. The role of intramolecular structural regularity in the in vitro and in vi vo antiviral activity of polyribonucleotide duplexes is discussed. (C) 1998 Elsevier Science B.V. All rights reserved.