Emerging technologies for making glycan-defined glycoproteins

ACS Chem Biol. 2012 Jan 20;7(1):110-22. doi: 10.1021/cb200429n. Epub 2011 Dec 14.

Abstract

Protein glycosylation is a common and complex posttranslational modification of proteins, which expands functional diversity while boosting structural heterogeneity. Glycoproteins, the end products of such a modification, are typically produced as mixtures of glycoforms possessing the same polypeptide backbone but differing in the site of glycosylation and/or in the structures of pendant glycans, from which single glycoforms are difficult to isolate. The urgent need for glycan-defined glycoproteins in both detailed structure-function relationship studies and therapeutic applications has stimulated an extensive interest in developing various methods for manipulating protein glycosylation. This review highlights emerging technologies that hold great promise in making a variety of glycan-defined glycoproteins, with a particular emphasis in the following three areas: specific glycoengineering of host biosynthetic pathways, in vitro chemoenzymatic glycosylation remodeling, and chemoselective and site-specific glycosylation of proteins.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • CHO Cells
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Cricetinae
  • Escherichia coli
  • Gene Expression
  • Glycoconjugates / chemical synthesis
  • Glycoconjugates / metabolism
  • Glycoproteins / genetics
  • Glycoproteins / metabolism*
  • Glycosylation
  • HEK293 Cells
  • Humans
  • Isomerism
  • Models, Molecular
  • Molecular Sequence Data
  • Plant Cells
  • Polysaccharides / chemistry*
  • Polysaccharides / metabolism
  • Protein Engineering / methods*
  • Protein Processing, Post-Translational*
  • Protein Structure, Secondary
  • Structure-Activity Relationship
  • Yeasts

Substances

  • Glycoconjugates
  • Glycoproteins
  • Polysaccharides