Molecular Pharmacology, Vol 12, 234-241, Copyright © 1976 by the American Society for Pharmacology and Experimental Therapeutics

Inhibition of Synthesis of Murine Leukemia Virus in Cultured Cells by Polyribonucleotides and Their 2'-O-Alkyl Derivatives

¹ Department of Medical Viral Oncology, Roswell Park Memorial Institute, and Graduate Faculty in Microbiology, State University of New York at Buffalo, Roswell Park Division, Buffalo, New York 14263
² Department of Biochemical and Biophysical Sciences, School of Hygiene and Public Health, The Johns Hopkins University, Baltimore, Maryland 21205

Poly(adenylic acid) [poly(A)], poly(inosinic acid) [poly(I)], poly(uridylic acid) [poly(U)], and poly(cytidylic acid) [poly(C)]inhibit the synthesis of Moloney murine leukemia virus in cultured JLS-V9 cells. The potency of inhibition depends on the base composition; poly(I) is more potent than poly(A) and poly(U), and poly(C) yields only a marginal relative inhibition. 2'-O-Alkyl polynucleotides show an enhanced inhibitory potency relative to the parent polynucleotides, and this enhancement is more marked for pyrimidine than for purine polynucleotides. These polynucleotides do not affect the population growth rates of normal cells; thus inhibition of virus synthesis apparently is not due to any cytotoxicity of polynucleotides for normal cells. The following order of inhibitory potency is observed: poly(I) > poly(A) > poly(U) > poly(C); poly(2'-O-methylmosinic acid) [poly(Im)] > poly(2'-O-methyl-uridylic acid) [poly(Um)] > poly(2'-O-ethyl-adenylic acid) [poly(Ae)] > poly(Am) [unknown] poly(2'-O-methyl-cytidylic acid) [poly(Cm)]; and poly(Im) > poly(I), poly(Am) > poly(A), poly(Um) > poly(U), poly(Cm) > poly(C).

Note:
ACKNOWLEDGMENTS We thank Mr. L. R. Davis for technical assistance, and Dr. R. J. Eckner for providing the leukemic spleen extract.