1H NMR study of the sugar pucker of 2',3'-dideoxynucleosides with anti-human immunodeficiency virus (HIV) activity.
The sugar ring conformations of 2',3'-dideoxyribosyladenine (ddA), 2',3'-dideoxyribosylcytosine (ddC), 2',3'-dideoxyribosylguanine (ddG), 2',3'-dideoxyribosylhypoxanthine (ddI), 3'-azido-2',3'-dideoxyribosylthymine (AZT), 3'-azido-2',3'-dideoxyribosyluracil (AZU) and 3'-fluoro-2',3'-dideoxyribosylthymine (FddT) have been investigated by 1H NMR spectroscopy. While the sugar ring in FddT exists almost totally in C2'-endo geometry, other nucleosides show equilibrium between sugar puckers of C3'-endo family (N-type) and C2'-endo family (S-type). For unsubstituted dideoxynucleosides C3'-endo conformer is favoured (congruent to 75%), whereas for AZT and AZU both the conformers have almost equal populations. Unlike X-ray diffraction studies, the NMR results do not support the suggestion that C3'-exo sugar puckers are desirable for the anti-HIV activity of these nucleosides.
Jagannadh
B
B
Indian Institute of Chemical Technology, Hyderabad, India.
Reddy
D V
DV
Kunwar
A C
AC
D000998:Antiviral Agents; D015224:Dideoxynucleosides / Q000737:chemistry* / Q000494:pharmacology; D006678:HIV / Q000187:drug effects*; D006859:Hydrogen; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008968:Molecular Conformation; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D000998:Antiviral Agents; D015224:Dideoxynucleosides; D006859:Hydrogen