Synthetic approaches to nuclease-resistant, nonnatural dinucleotides of anti-HIV integrase interest.
New, nonnatural dinucleotide 5'-monophosphates with a surrogate isonucleoside component of L-related stereochemistry, have been synthesized. Structures of the target compounds were confirmed by multinuclear NMR spectra (1H, 13C, 31P, COSY), UV hypochromicity, FAB HRMS data and X-ray crystallography. These compounds are totally resistant to cleavage by 3'- and 5'-exonucleases. Dinucleotides of this study with a terminal L-isonucleoside component 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 this type of selectivity of inhibition of the strand transfer step.
Chi
Guochen
G
Department of Pharmaceutical and Biomedical Sciences and The Center for Drug Discovery, University of Georgia, Athens, Georgia 30602, USA.
Nair
Vasu
V
D018360:Crystallography, X-Ray; D003851:Deoxyribonucleases / Q000737:chemistry*; D015226:Dinucleoside Phosphates / Q000138:chemical synthesis* / Q000737:chemistry; D019427:HIV Integrase / Q000737:chemistry*; D019428:HIV Integrase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure
D015226:Dinucleoside Phosphates; D019428:HIV Integrase Inhibitors; D019427:HIV Integrase; D003851:Deoxyribonucleases