A Comparison of the Conformations of the 5′-Triphosphates of Zidovudine (AZT) and Thymidine Bound to HIV-1 Reverse Transcriptase

Abstract

Nuclear Overhauser effect experiments were performed at 500 MHz to determine the conformations of AZTTP and dTTP when bound to HIV- 1 reverse transcriptase. The conformations of both ligands were found to be similar in the bound state. The orientation of the glycosidic angle is anti (χ = −120° ± 12 for AZTTP and −110° ± 12 for dTTP), γ is +sc and the pucker of the 3′-azido-2′,3′-dideoxy- and 2′-deoxyribose rings is predominantly C4′ exo(P = 60° ± 10 for AZTTP and 55° ± 8 for dTTP). These results indicate that the unusual C4′endo/C3′exo pucker (P = 215°) reported for the dideoxyribose ring of AZT in the solid state does not play a role in the interaction of HIV- 1 reverse transcriptase with AZTTP.