Total Synthesis of Core 3 & Core 4-Type Mucin Glycan Derivatives

Abstract

Recent studies have demonstrated the ability of mucin O-glycans to attenuate virulence in diverse, cross-kingdom pathogens, sparking interest in their development as a novel therapeutic approach against infection. Although their virulence attenuating activity is evident, mucin glycans obtained from native sources comprise mixtures of several hundred distinct structures, and therefore the specific active glycan epitopes and molecular mechanisms of virulence attenuation remain unclear. Individual mucin glycan structures cannot be purified from native sources and are not amenable to automated synthesis; therefore, to further investigate the phenomena of virulence attenuation we have been developing convergent and scalable methods (>30 mg per target glycan) to assemble a mucin O-glycan library in sufficient scale and purity to facilitate biological studies. Previously we described a method to obtain core 1 & core 2-type mucin glycan derivatives that have since been used to identify active epitopes in Candida albicans and Vibrio cholerae. In the current study, we describe the expansion of our glycan library to include core 3 & core 4-type derivatives, increasing the structural diversity of our platform for biological evaluation.