Kovács T, Párkányi L, Pelczer I, Cervantes-Lee F, Pannell K H, Torrence P F
Biomedical Chemistry Section, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
J Med Chem. 1991 Aug;34(8):2595-600. doi: 10.1021/jm00112a038.
The recent finding that 3'-amino-3'-deoxythymidine 5'-triphosphate is a noncompetitive inhibitor of the HIV-1 reverse transcriptase (Kedar, P.S.; et al. Biochemistry 1990, 29, 3603-3611), prompted an investigation of the conformation of 3'-amino-3'-deoxythymidine. An X-ray diffraction study has revealed that the glycosidic torsion angle of the nucleoside is in the less common syn region and this solid-state geometry is stabilized by a three-dimensional network of self-associated hydrogen-bonded molecules. On the other hand, the aqueous solution conformation, as determined by 1H NMR, places the glycosidic torsion angle in the more usual anti region with the sugar in an equilibrium between C3'-endo and C2'-endo puckering. The energy barrier between the solid-state and solution conformation is relatively low as was demonstrated by the MM2 calculations.
最近发现3'-氨基-3'-脱氧胸苷5'-三磷酸是HIV-1逆转录酶的非竞争性抑制剂（凯达尔，P.S.等人，《生物化学》，1990年，29卷，3603 - 3611页），这促使人们对3'-氨基-3'-脱氧胸苷的构象进行研究。一项X射线衍射研究表明，该核苷的糖苷扭转角处于不太常见的顺式区域，并且这种固态几何结构通过自缔合氢键分子的三维网络得以稳定。另一方面，通过1H NMR确定的水溶液构象中，糖苷扭转角处于更常见的反式区域，糖在C3'-内型和C2'-内型褶皱之间处于平衡状态。MM2计算表明，固态和溶液构象之间的能垒相对较低。
