4-Thio-uridylate (UD29) interferes with the function of protein -SH and inhibits HIV replication in vitro.
In this short communication, it is shown that 4-thio-uridylate (s(4)UMP, designated as UD29) inhibits glyceraldehyde 3-phosphate dehydrogenase (GAPDH), suggesting that the enol-form of the thiolated nucleotide may interfere with the function of the essential -SH group in the active center of the enzyme. Since HIV entry requires thiol/disulfide exchange processes, this activity prompted us to study the anti-HIV activity of the nucleotide. Indeed, UD29 inhibited the replication of HIV-1(IIIB) in the MT-4 cell line and HIV-1(Ada-M) in peripheral blood mononuclear cells (PBMC). Furthermore, UD29 was not toxic in PBMCs in vitro or in mice when the compound was administered intravenously.
Beck
Zoltán
Z
Department of Medical Microbiology, Medical and Health Science Center, Faculty of Medicine, University of Debrecen, Nagyerdei krt. 98, Debrecen H 4012, Hungary.
Kis
Andrea
A
Berényi
Erika
E
Kovács
Péter
P
Fésüs
László
L
Aradi
János
J
D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases / Q000037:antagonists & inhibitors*; D015497:HIV-1 / Q000187:drug effects*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D013438:Sulfhydryl Compounds / Q000378:metabolism*; D013873:Thionucleotides / Q000494:pharmacology*; D014542:Uridine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects*
D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D013438:Sulfhydryl Compounds; D013873:Thionucleotides; C009473:4-thiouridylic acid; D014542:Uridine Monophosphate; D005987:Glyceraldehyde-3-Phosphate Dehydrogenases