5-甲氧基甲基-2'-脱氧尿苷与5-甲氧基甲基-1-(2'-脱氧-β-D-呋喃来苏糖基)尿嘧啶的结构与抗病毒活性之间的关系

Relationship between structure and antiviral activity of 5-methoxymethyl-2'-deoxyuridine and 5-methoxymethyl-1-(2'-deoxy-beta-D-lyxofuranosyl)uracil.

作者信息

Gupta S V, Tourigny G, Stuart A L, De Clercq E, Quail J W, Ekiel I, el-Kabbani O A, Delbaere L T

出版信息

Antiviral Res. 1987 Feb;7(2):69-77. doi: 10.1016/0166-3542(87)90022-2.

Abstract

5-Methoxymethyl-1-(2'-deoxy-beta-D-lyxofuranosyl)uracil (MMdLU) was not active against the herpes simplex viruses. The relationship between molecular conformation and antiviral activity for the two epimers, 5-methoxymethyl-2'-deoxyuridine (MMdUrd) and MMdLU, is discussed. MMdUrd was phosphorylated by the virus-induced deoxythymidine kinase. In contrast, MMdLU did not serve as a substrate for the kinase. The geometry and distance between the 5'-CH2OH and 3'-OH groups of the furanose ring appear to be key factors in determining the efficiency of phosphorylation by the virus-induced deoxythymidine kinase, and hence antiviral activity.

摘要

5-甲氧基甲基-1-(2'-脱氧-β-D-来苏呋喃糖基)尿嘧啶(MMdLU)对单纯疱疹病毒无活性。讨论了两种差向异构体5-甲氧基甲基-2'-脱氧尿苷(MMdUrd)和MMdLU的分子构象与抗病毒活性之间的关系。MMdUrd被病毒诱导的脱氧胸苷激酶磷酸化。相比之下，MMdLU不是该激酶的底物。呋喃糖环5'-CH2OH和3'-OH基团之间的几何形状和距离似乎是决定病毒诱导的脱氧胸苷激酶磷酸化效率的关键因素，从而也是决定抗病毒活性的关键因素。