NMR-STUDY OF DIDEOXYNUCLEOTIDES WITH ANTI-HUMAN-IMMUNODEFICIENCY-VIRUS (HIV) ACTIVITY

The molecular structures of 3'-azido-2',3'-dideoxyribosylthymine 5'-tr iphosphate (AZTTP), 2',3'-dideoxyribosylinosine 5'-triphosphate (ddITP ), 3'-azido-2',3'-dideoxyribosylthymine 5'-monophosphate (AZTMP) and 2 ',3'-dideoxyribosyladenine 5'-monophosphate (ddAMP) have been studied by NMR to understand their anti-HIV activity. For ddAMP and ddITP, con formations are almost identical with their nucleoside analogues with s ugar ring pucker equilibriating between C3'-endo (similar to 75%) and C2'-endo (similar to 25%). AZTMP and AZTTP bn the other hand show sign ificant variations in the conformational behaviour compared with 3'-az ido-2',3'-dideoxyribosylthymine (AZT). The sugar rings for these nucle otides have a much larger population of C2'-endo (similar to 75%) conf ormers, like those observed for natural 2'-deoxynucleosides and nucleo tides. The major conformers around C5'-O5', C4'-C5' and the glycosidic bonds are the beta(t), gamma(+) and anti, respectively.