The anti-conformation of 2',3'-dideoxy nucleosides may be essential for anti-HIV activity: evidence from the crystal structure of 2',3'-dideoxy formycin A.
The crystal structure of the nucleoside 2',3'-dideoxyformycin A has been determined. The structure shows a syn conformation about the glycosidic bond, stabilised by an intramolecular hydrogen bond between the 05' and N3 atoms. HIV activity was examined in a syncytium inhibition assay. In contrast to the marked decrease in viral titre observed with 2',3'-dideoxycytidine, the formycin analogue produced no effect. It may be concluded that the syn conformation for a dideoxy nucleoside is probably deleterious to HIV inhibition of HIV replication.
Neidle
S
S
Cancer Research Campaign Biomolecular Structure Unit, Institute of Cancer Research, Sutton, Surrey, U.K.
Urpi
L
L
Serafinowski
P
P
Whitby
D
D
D000998:Antiviral Agents; D003461:Crystallography; D015224:Dideoxynucleosides; D006678:HIV / Q000187:drug effects; D008958:Models, Molecular; D009690:Nucleic Acid Conformation; D013329:Structure-Activity Relationship; D014961:X-Ray Diffraction
D000998:Antiviral Agents; D015224:Dideoxynucleosides; C060054:2',3'-dideoxyformycin A