Wang J, Froeyen M, Hendrix C, Andrei G, Snoeck R, De Clercq E, Herdewijn P
Laboratories of Medicinal Chemistry and of Virology and Chemotherapy, Rega Institute for Medical Research, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
J Med Chem. 2000 Feb 24;43(4):736-45. doi: 10.1021/jm991171l.
Both enantiomers of cyclohexenylguanine were synthesized in a stereospecific way starting from the same starting material: R-(-)-carvone. Both compounds showed potent and selective anti-herpesvirus activity (HSV-1, HSV-2, VZV, CMV). The binding of both cyclohexene nucleosides in the active site of HSV-1 thymidine kinase was investigated, and a model for the binding of both enantiomers is proposed. The amino acids involved in binding of the optical antipodes are the same, but the interaction energy of both enantiomers is slightly different. This may be attributed to the interaction of the secondary hydroxyl function of the nucleoside analogues with Glu-225. Structural analysis has demonstrated the flexibility of the cyclohexenyl system, and this may be considered as an important conformational characteristic explaining the potent antiviral activity.
R-(-)-香芹酮合成。两种化合物均表现出强效且选择性的抗疱疹病毒活性（HSV-1、HSV-2、VZV、CMV）。研究了两种环己烯核苷在HSV-1胸苷激酶活性位点的结合情况，并提出了两种对映体的结合模型。参与光学对映体结合的氨基酸相同，但两种对映体的相互作用能略有不同。这可能归因于核苷类似物的仲羟基官能团与Glu-225的相互作用。结构分析表明环己烯基系统具有灵活性，这可被视为解释其强效抗病毒活性的重要构象特征。
