The effect of the 3'-OH group on the conformation and binding ability of anhydropyrimidine nucleosides to uridine phosphorylase.

Abstract 2,2′-Anhydro-3′-deoxy-5-ethyluridine, a new pyrimidine nucleoside analog, has been examined in terms of its binding potency to uridine phosphorylase, and its conformation in solution (NMR) was studied. 2,2′-Anhydro-3′-deoxy-5-ethyluridine has a K i value of 3.4 μ m for uridine phosphorylase from rat intestinal mucosa. This value is approximately one order of magnitude lower than the K m for uridine (22 μ m ), the natural substrate. The presence of the 3′-OH group (in the ribo-configuration) on pyrimidine nucleoside analogs may not be considered a prerequisite for the binding to uridine phosphorylase; however, it enhances the binding in the case of flexible ligands cooperating in the process of conformation change toward a more favorable enzyme-ligand interaction. The presence of the 3′-OH group in pyrimidine nucleosides seems to be essential if the molecule is to become a substrate.