Enantio-Selectivity of Human Nucleoside Monophosphate Kinases

Abstract

Over recent years, there has been a renewed interest in the development of l-nucleosides as safe and efficacious drugs for the treatment of viral infections. Biological activity of these compounds requires phosphorylation to their triphosphate form, involving nucleoside monophosphate kinases in the second step. In order to characterize the activation pathway of l-nucleosides of the pyrimidine series, we studied the enantio-selectivity of human uridylate-cytidylate and thymidylate kinases. The results showed that these enzymes are only weakly enantio-selective and are thus probably involved in the activation of l-nucleosides in vivo. An activation pathway for telbivudine (l-dT) was therefore proposed.

Keywords:

• Structure activity relationship
• human NMP kinases
• HBV
• l-dT

These studies were supported by a grant from the Agence nationale pour la Recherche (ANR) France.