Inhibition of the strand transfer step of HIV-1 integrase by non-natural dinucleotides.
New, non-natural dinucleotide 5'-monophosphates, with a surrogate isonucleoside component of l-related stereochemistry at the 'terminal' position, have been synthesized. Structures of 2a-c were confirmed by multinuclear NMR spectra ((1)H, (13)C, (31)P, COSY), UV hypochromicity and FAB HRMS data. These compounds are totally resistant to cleavage by 3'- and 5'-exonucleases. The dinucleotides showed remarkable selectivity for inhibition of the strand transfer step of HIV-1 integrase. To the best of our knowledge, these compounds represent only the second example of selective strand transfer inhibitors of HIV integrase.
Chi
Guochen
G
Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA.
Neamati
Nouri
N
Nair
Vasu
V
D015226:Dinucleoside Phosphates / Q000138:chemical synthesis* / Q000494:pharmacology; D019427:HIV Integrase / Q000187:drug effects*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
D015226:Dinucleoside Phosphates; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase