Use of click chemistry to define the substrate specificity of Leishmania β-1,2-mannosyltransferases

Abstract

Leishmania spp. are human pathogens that utilize a novel β-7,2-mannan as their major carbohydrate reserve material. We describe a new approach that combines traditional substrate-modification methods and "click chemistry" to assemble a library of modified substrates that were used to qualitatively define the substrate tolerance of the Leishmania β-1,2-mannosyltransferases responsible for β-1,2-mannan biosynthesis. The library was assembled by using the highly selective copper(I)-catalysed cycloaddition reaction of azides and alkynes to couple an assortment of azide- and alkyne-functionalized small molecules with complementary alkyne- and azide-functionalized mannose derivatives. All mannose ..