Total Synthesis of Homogeneous Glycopeptides and Glycoproteins

Abstract

Glycosylation is a ubiquitous post-translational modification of proteins. Access to pure glycoproteins is extremely challenging owing to the enzymatic glycosylation process which is not templated and, as such, affords heterogeneous mixtures of glycoforms. Chemical synthesis provides an attractive avenue to access homogeneously glycosylated peptides and proteins, thus providing a means to elucidate the role of specific glycan modifications on structure and function. This thesis outlined the development of a number of novel synthetic methods to access biologically important glycopeptides and glycoproteins in pure form. Examples would include the synthesis of an unusual glycan modification of arginine which is present on key proteins from pathogenic bacteria and the synthesis of a library of homogenously glycosylated chemokines and cytokines. The results from these studies would inform new anti-infective and anti-inflammatory strategies in the future.