Inhibition of HIV integrase by novel nucleotides bearing tricyclic bases.
5'-Monophosphates of several novel dideoxynucleosides bearing tricyclic nucleobases were synthesized. Both linear and angular ring-extended analogs of isomeric dideoxyadenosine 5'-monophosphate were discovered to have moderate to good inhibition of the viral-encoded enzyme, HIV integrase. The results suggest that the nucleotide binding site of HIV integrase can accommodate major modifications in the nucleobase, which is in stark contrast to the nucleotide binding site on HIV reverse transcriptase.
Zhang
J
J
Department of Chemistry, University of Iowa, Iowa City 52242, USA.
Neamati
N
N
Pommier
Y
Y
Nair
V
V
D019380:Anti-HIV Agents / Q000737:chemistry / Q000494:pharmacology*; D003838:Deoxyadenine Nucleotides / Q000737:chemistry / Q000494:pharmacology*; D054306:Dideoxynucleotides; D019428:HIV Integrase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D015497:HIV-1 / Q000187:drug effects / Q000201:enzymology
D019380:Anti-HIV Agents; D003838:Deoxyadenine Nucleotides; D054306:Dideoxynucleotides; D019428:HIV Integrase Inhibitors; C010110:2',3'-dideoxyadenosine 5'-phosphate