NMR study of dideoxynucleotides with anti-human immunodeficiency virus (HIV) activity.
The molecular structures of 3'-azido-2',3'-dideoxyribosylthymine 5'-triphosphate (AZTTP), 2',3'-dideoxyribosylinosine 5'-triphosphate (ddlTP), 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, conformations are almost identical with their nucleoside analogues with sugar ring pucker equilibriating between C3'-endo (approximately 75%) and C2'-endo (approximately 25%). AZTMP and AZTTP on the other hand show significant variations in the conformational behaviour compared with 3'-azido-2',3'-dideoxyribosylthymine (AZT). The sugar rings for these nucleotides have a much larger population of C2'-endo (approximately 75%) conformers, like those observed for natural 2'-deoxynucleosides and nucleotides. The major conformers around C5'-O5', C4'-C5' and the glycosidic bonds are the beta 1, gamma + and anti, respectively.
Reddy
D V
DV
Indian Institute of Chemical Technology, Hyderabad, India.
Jagannadh
B
B
Kunwar
A C
AC
D000998:Antiviral Agents / Q000737:chemistry* / Q000494:pharmacology; D054306:Dideoxynucleotides; D006678:HIV / Q000187:drug effects*; D006801:Humans; D007293:Inosine Triphosphate / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008962:Models, Theoretical; D008968:Molecular Conformation; D015394:Molecular Structure; D013942:Thymine Nucleotides / Q000737:chemistry* / Q000494:pharmacology; D015215:Zidovudine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology
D000998:Antiviral Agents; D054306:Dideoxynucleotides; D013942:Thymine Nucleotides; C099971:2',3'-dideoxyribosylinosine 5'-triphosphate; D007293:Inosine Triphosphate; C057287:3'-azido-3'-deoxythymidine 5'phosphate; D015215:Zidovudine; C052873:zidovudine triphosphate