Recent Development in Ligation Methods for Glycopeptide and Glycoprotein Synthesis

Abstract

Glycoproteins are produced by the post‐translational modification process of proteins and they play an important role in mediating various biological processes. Our understanding towards biochemical functions of individual glycoproteins has been seriously hampered due to the heterogeneous expression of carbohydrate parts in glycoproteins. Despite the advancement in recombinant expression and chromatographic techniques, the isolation of pure glycoforms remains nearly impossible. To obtain homogenous glycoproteins, tremendous efforts hves been spent in developing various ligation and glycosylation techniques. This minireview discusses selected methods for the preparation and ligation of glycopeptides. The importance of the development of new chemical synthesis method for glycoproteins has also been discussed, which would be one of the next directions in this field.

Rapid building block-economic synthesis of long, multi-O-GalNAcylated MUC5AC tandem repeat peptides

“…The arguably most robust access to long peptides is provided by native chemical ligation. [36][37][38][39] MUC5AC contains multiple copies of a Thr-and Ser-rich octapeptide TR, with TTSTTSXP as a typical representative. 4 Considering the absence of cysteine and the occurrence of Ala as a frequently occurring amino acid at position X, we targeted a Ser-Cys junction, which can be converted to the native Ser-Ala junction by desulfurization.…”

Carbohydrate-Based Macromolecular Biomaterials

“…In the former type, glycans are conjugated to hydroxyl groups of amino acid (serine, threonine, or tyrosine) residues, while the latter are glycoproteins with glycans attached to amide side chain of asparagine. 122 For example, mucins are highly glycosylated proteins that are abundant in the mucus of humans and animals. They play important physiological roles, such as cell adhesion and signaling, immune response, and so on.…”

“…Natural glycoproteins can be divided into O -linked glycoproteins and N -linked glycoproteins. In the former type, glycans are conjugated to hydroxyl groups of amino acid (serine, threonine, or tyrosine) residues, while the latter are glycoproteins with glycans attached to amide side chain of asparagine . For example, mucins are highly glycosylated proteins that are abundant in the mucus of humans and animals.…”

Silver-promoted solid-phase guanidinylation enables the first synthesis of arginine glycosylated Samoamide A cyclopeptide analogue

“…For N-linked glycopeptides, the main research is focused on the glycosylation of asparagine. In addition to using preformed glycosyl amino acids to synthesize glycopeptides, we can also use convergence strategies to directly glycosylate peptide chains to produce glycosylated peptides, called Lansbury’s aspartylation ( Li and Zhu, 2016 ; Lin and Liu, 2020 ). Later, with the discovery that arginine can also be induced glycosylation, researchers also began to study the method of synthesizing arginine glycosylation.…”