Hydroxymethylbenzimidazole carboxylic acid models of the Asp-His-Ser charge relay system of serine proteases

Abstract

2-Hydroxymethyl- and 2-acetoxymethylbenzimidazole, and their C-4(7)-carboxy derivatives, have been synthesized and characterized for evaluation as chemical models of the Asp-His-Ser triad present at the active sites of several serine proteases. Preliminary studies of the 2-acetoxy compounds, which are analogues of the acyl enzymes, show that the rate of hydrolysis is augmented only 2.5 fold by the carboxylate group of the model charge relay system.