Relationship between structure and antiviral activity of 5-methoxymethyl-2'-deoxyuridine and 5-methoxymethyl-1-(2'-deoxy-beta-D-lyxofuranosyl)uracil.
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.
D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D002460:Cell Line; D055598:Chemical Phenomena; D002621:Chemistry; D003857:Deoxyuridine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006367:HeLa Cells; D006801:Humans; D018139:Simplexvirus / Q000187:drug effects* / Q000201:enzymology; D012984:Software; D013329:Structure-Activity Relationship; D013937:Thymidine Kinase / Q000378:metabolism
D000998:Antiviral Agents; C052249:5-methoxymethyl-1-(2'-deoxylyxofuranosyl)uracil; C024722:5-methoxymethyl-2'-deoxyuridine; D013937:Thymidine Kinase; D003857:Deoxyuridine