Discovery of a nuclease-resistant, non-natural dinucleotide that inhibits HIV-1 integrase.
Integration of HIV viral DNA into human chromosomal DNA catalyzed by HIV integrase is essential for the replication of HIV. Discovery of novel inhibitors of HIV integrase is of considerable significance in approaches to the development of therapeutic agents against AIDS. We have synthesized a new dinucleotide 1 with an internucleotide phosphate bond that is unusually resistant to exonucleases. This compound exhibits potent anti-HIV-1 integrase activity.
Taktakishvili
M
M
Department of Chemistry, The University of Iowa, Iowa City, IA 52242, USA.
Neamati
N
N
Pommier
Y
Y
Nair
V
V
D004279:DNA, Viral / Q000378:metabolism; D005092:Exonucleases / Q000378:metabolism*; D019427:HIV Integrase / Q000187:drug effects / Q000378:metabolism*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D008968:Molecular Conformation; D009711:Nucleotides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
D004279:DNA, Viral; D019428:HIV Integrase Inhibitors; D009711:Nucleotides; D019427:HIV Integrase; D005092:Exonucleases