The role of 2',3'-unsaturation on the antiviral activity of anti-HIV nucleosides against 3TC-resistant mutant (M184V).
Molecular modeling studies show that the 2',3'-double bond of the sugar moiety of various 2',3'-unsaturated nucleosides interacts with the aromatic moiety of Tyr115 of HIV-1 reverse transcriptase (RT) by hydrophobic pi-pi interaction. In 3TC-resistant mutant (M184V) RT, 2'-fluoro-2',3'-unsaturated nucleosides with a bulky 4'-substituent experience significant steric hindrance with the side chain of Val184.
Choo
Hyunah
H
Department of Pharmaceutical and Biomedical Sciences, College of Pharmacy, The University of Georgia, Athens, GA 30602, USA.
Chong
Youhoon
Y
Chu
Chung K
CK
D019943:Amino Acid Substitution; D019380:Anti-HIV Agents / Q000737:chemistry* / Q000494:pharmacology*; D024882:Drug Resistance, Viral; D054303:HIV Reverse Transcriptase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D015497:HIV-1 / Q000187:drug effects* / Q000201:enzymology / Q000235:genetics; D019259:Lamivudine / Q000494:pharmacology; D008958:Models, Molecular; D008968:Molecular Conformation; D009154:Mutation; D009705:Nucleosides / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology*; D018894:Reverse Transcriptase Inhibitors / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
D019380:Anti-HIV Agents; D009705:Nucleosides; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D014443:Tyrosine; D054303:HIV Reverse Transcriptase