title: Design and synthesis of specific inhibitors of the 3'-processing step of HIV-1 integrase.
abstract: The novel dinucleotide 5'-phosphate, [(L,D)-pIsodApdC], discovered in our laboratory, is a strong inhibitor of HIV-1 integrase for both the 3'-processing and the strand transfer steps. The rationale used in this molecular design was that residues immediately upstream of the dinucleotide cleavage site in the 3'-processing step might provide critical recognition/binding sites on integrase. The rationale for the second type of inhibitors was based on the elimination products (linear and cyclic dinucleotides) of 3'-processing. However, while the linear dinucleotide 5'-phosphate (pdGpdT) was active, its cyclic counterpart was inactive against both wild-type and mutant HIV integrase.
authors.affiliation: Department of Pharmaceutical and Biomedical Sciences, The University of Georgia, Athens, Georgia, 30602, USA.
authors.forename: Guochen
authors.initials: G
authors.lastname: Chi
authors.forename: Byung I
authors.initials: BI
authors.lastname: Seo
authors.forename: Vasu
authors.initials: V
authors.lastname: Nair
mesh_terms: D019380:Anti-HIV Agents / Q000494:pharmacology*; D001665:Binding Sites; D002626:Chemistry, Pharmaceutical / Q000379:methods; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D019427:HIV Integrase / Q000737:chemistry; D019428:HIV Integrase Inhibitors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D009711:Nucleotides / Q000737:chemistry; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D019380:Anti-HIV Agents; D004791:Enzyme Inhibitors; D019428:HIV Integrase Inhibitors; D009711:Nucleotides; D011994:Recombinant Proteins; D019427:HIV Integrase