Glycoconjugate synthesis using chemoselective ligation

Protein glycosylation plays critical roles in many biological processes. However, the fundamental study and application of glycobiology are hindered by the heterogeneousness of oligosaccharides in natural glycoproteins and the difficulty in constructing glycoproteins of human design. Herein, we describe a semisynthetic method to site‐specifically modify proteins with reducing carbohydrates. The method involves the genetic incorporation of a side‐chain‐esterified aspartate, which was subsequently quantitatively converted into alanine‐β‐hydrazide (Aβz), and chemoselective conjugation of Aβz with a range of readily available reducing carbohydrates. The resulting Aβz‐linked GlcNAc is a close mimic of native N‐GlcNAc and could be installed on various proteins, including IL‐17A and RNase A. Notably, Aβz‐linked GlcNAc on proteins reacted with biantennary oligosaccharide oxazoline derivatives through endoglycosidase‐catalyzed transglycosylation reactions to enable the assembly of homogeneous glycans on proteins.

show abstract

Site‐Specific Protein Modification with Reducing Carbohydrates

Dong

Miao

et al. 2022

Angew Chem Int Ed

View full text Add to dashboard Cite

Protein glycosylation plays critical roles in many biological processes. However, the fundamental study and application of glycobiology are hindered by the heterogeneousness of oligosaccharides in natural glycoproteins and the difficulty in constructing glycoproteins of human design. Herein, we describe a semisynthetic method to site-specifically modify proteins with reducing carbohydrates. The method involves the genetic incorporation of a side-chain-esterified aspartate, which was subsequently quantitatively converted into alanine-β-hydrazide (Aβz), and chemoselective conjugation of Aβz with a range of readily available reducing carbohydrates. The resulting Aβz-linked GlcNAc is a close mimic of native N-GlcNAc and could be installed on various proteins, including IL-17A and RNase A. Notably, Aβz-linked GlcNAc on proteins reacted with biantennary oligosaccharide oxazoline derivatives through endoglycosidase-catalyzed transglycosylation reactions to enable the assembly of homogeneous glycans on proteins.

show abstract

Glycoconjugate synthesis using chemoselective ligation

Abstract: Chemoselective ligation of carbohydrates and polypeptides was achieved using an adipic acid dihydrazide cross-linker.

Cited by 15 publications

References 31 publications

Peptide Glycosides

Peptide Glycosides

Site‐Specific Protein Modification with Reducing Carbohydrates

Site‐Specific Protein Modification with Reducing Carbohydrates

Contact Info

Product

Resources

About