Synthesis and Application of Glycopeptide and Glycoprotein Mimetics

Abstract

Glycosylation of proteins is the most complex form of posttranslational modification. Glycan chains of glycoproteins are involved in numerous biological recognition events, such as protein folding, cell cell communication and adhesion, cell growth and differentiation, as well as bacterial and viral infection. As an alternative to glycoprotein synthesis, approaches to the construction of glycopeptide and glycoprotein mimetics have been developed. These so-called neoglycopeptides and neoglycoproteins, respectively, provide insight on the importance of distinct structural elements on biological activity. Furthermore, they may have improved properties, such as increased stability in the case of S- and C-glycopeptides. This article summarizes recent progress in the field of synthetic glycosylated amino acids, peptides, and proteins with non-natural structural elements with a focus on the carbohydrate peptide linkage. Linear and convergent approaches are discussed. Application of chemoselective ligation reactions provides access to pure glycoforms of glycoprotein mimetics.