Glyco-based building blocks for the chemical synthesis of glycoproteins.

Glycoproteins, which are conjugates of glycans and proteins, are crucial in a wide variety of physiological and disease processes. Understanding the structures and functions of glycoproteins, as well as the regulation of glycosylation, is essential for studying the causes of diseases for intervention therapy. However, the detailed structure-function relationships and therapeutic applications of glycoproteins are hindered by their structural complexity and heterogeneity. Chemical protein synthesis is a powerful and effective strategy for producing homogeneous glycoforms of glycoproteins. The chemical synthesis of glycoproteins involves ligating different peptide and/or glycopeptide fragments, and the preparation of glycopeptide fragments requires the assembly of amino acid and glyco-based building blocks. This review provides a comprehensive and systematic survey of glyco-based building blocks for synthesizing homogeneous glycopeptides and glycoproteins, encompassing glyco-amino acids for direct SPPS and glyco-based donors for convergent sugar assembly. Additionally, an analysis of the applications of these building blocks in the chemical synthesis of representative glycoproteins with therapeutic potential is presented.