Glyco-analytical multispecific proteolysis (Glyco-AMP): a simple method for detailed and quantitative Glycoproteomic characterization

J Proteome Res. 2013 Oct 4;12(10):4414-23. doi: 10.1021/pr400442y. Epub 2013 Sep 20.

Abstract

Despite recent advances, site-specific profiling of protein glycosylation remains a significant analytical challenge for conventional proteomic methodology. To alleviate the issue, we propose glyco-analytical multispecific proteolysis (Glyco-AMP) as a strategy for glycoproteomic characterization. Glyco-AMP consists of rapid, in-solution digestion of an analyte glycoprotein (or glycoprotein mixture) by a multispecific protease (or protease cocktail). Resulting glycopeptides are chromatographically separated by isomer-specific porous graphitized carbon nano-LC, quantified by high-resolution MS, and structurally elucidated by MS/MS. To demonstrate the consistency and customizability of Glyco-AMP methodology, the glyco-analytical performances of multispecific proteases subtilisin, pronase, and proteinase K were characterized in terms of quantitative accuracy, sensitivity, and digestion kinetics. Glyco-AMP was shown be effective on glycoprotein mixtures as well as glycoproteins with multiple glycosylation sites, providing detailed, quantitative, site- and structure-specific information about protein glycosylation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Bacterial Proteins / chemistry
  • Carbohydrate Conformation
  • Carbohydrate Sequence
  • Chromatography, High Pressure Liquid
  • Glycoproteins / chemistry*
  • Glycosylation
  • Humans
  • Molecular Sequence Data
  • Peptide Fragments / chemistry
  • Peptide Fragments / isolation & purification
  • Peptide Hydrolases / chemistry*
  • Peptide Mapping
  • Polysaccharides / chemistry
  • Polysaccharides / isolation & purification
  • Protein Processing, Post-Translational*
  • Proteolysis
  • Proteomics
  • Ribonucleases / chemistry
  • Tandem Mass Spectrometry

Substances

  • Bacterial Proteins
  • Glycoproteins
  • Peptide Fragments
  • Polysaccharides
  • Ribonucleases
  • ribonuclease B
  • Peptide Hydrolases