Open AccessComparative inhibition of hepatitis B virus DNA polymerase and cellular DNA polymerases by triphosphates of sugar-modified 5-methyldeoxycytidines and of other nucleoside analogs
Author(s) -
E. Matthes,
K. Reimer,
Martin von JantaLipinski,
Helga Meisel,
Christian Lehmann
Publication year - 1991
Publication title -
antimicrobial agents and chemotherapy
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.07
H-Index - 259
eISSN - 1070-6283
pISSN - 0066-4804
DOI - 10.1128/aac.35.6.1254
Subject(s) - dna polymerase , polymerase , nucleoside , hepatitis b virus dna polymerase , dna , microbiology and biotechnology , hepatitis b virus , biology , nucleoside analogue , virology , biochemistry , chemistry , virus
Of a series of 14 nucleoside 5'-triphosphates, those of 2',3'-dideoxy-3'-fluoro-5-methylcytidine, 3'-azido-2',3'-dideoxy-5-methylcytidine, 2',3'-dideoxy-3'-fluoroguanosine, 2',3'-didehydro-2',3'-dideoxy-5-methylcytidine, 2',3'-dideoxy-3'-fluoro-5-ethylcytidine, and 2',3'-dideoxy-3'-fluoroadenosine emerged as the most potent inhibitors of hepatitis B virus DNA polymerase (50% inhibitory dose, 0.03 to 0.35 microM). In contrast, cellular DNA polymerases proved to be resistant to (alpha) or partially affected by (beta) these analogs. These compounds are among the most effective and selective inhibitors of endogenous hepatitis B virus DNA polymerase recognized to date.