Journal article

Exploration of Strategies for Mechanism-Based Inhibitor Design for Family GH99 endo--1,2-Mannanases

Pearl Z Fernandes, Marija Petricevic, Lukasz Sobala, Gideon J Davies, Spencer J Williams

CHEMISTRY-A EUROPEAN JOURNAL | WILEY-V C H VERLAG GMBH | Published : 2018

Abstract

endo-α-1,2-Mannosidases and -mannanases, members of glycoside hydrolase family 99 (GH99), cleave α-Glc/Man-1,3-α-Man-OR structures within mammalian N-linked glycans and fungal α-mannan, respectively. They are proposed to act through a two-step mechanism involving a 1,2-anhydrosugar "epoxide" intermediate incorporating two conserved catalytic carboxylates. In the first step, one carboxylate acts as a general base to deprotonate the 2-hydroxy group adjacent to the fissile glycosidic bond, and the other provides general acid assistance to the departure of the aglycon. We report herein the synthesis of two inhibitors designed to interact with either the general base (α-mannosyl-1,3-(2-aminodeoxy..

View full abstract

University of Melbourne Researchers