A practical approach to enrich intact tryptic N-glycopeptides through size exclusion chromatography and hydrophilicity (SELIC) using an acrylamide-agarose composite gel system

Anal Chim Acta. 2019 Jun 13:1058:107-116. doi: 10.1016/j.aca.2019.01.044. Epub 2019 Feb 1.

Abstract

Increasing researches proved that abnormal glycosylation is strongly correlated with many diseases. Specially, site-specific glycosylation and its associated heterogeneity are closely related to the function and activity of the glycoprotein. However, intact N-glycopeptide analysis still faces great challenges because the presence of highly abundant non-glycosylated peptides would suppress the ionization of lowly abundant glycopeptides. In the present study, we developed a practical intact tryptic N-glycopeptide enrichment method using acrylamide-agarose composite gel that combined the size exclusion chromatography and hydrophilic (named SELIC) effects, aimed to remove the detergent rapidly and effectively, as well as enrich intact N-glycopeptides while extracting peptides. This is a useful tool to facilitate the intact N-glycopeptides analysis of complex protein mixtures, particularly for samples that extracted from formalin-fixed and paraffin-embedded (FFPE) tissues by SDS. Using this method, we successfully identified 700 site-specific intact tryptic N-glycopeptides corresponding to 261 glycosylation sites on 191 glycoproteins from FFPE thymoma tissues.

Keywords: Acrylamide-agarose composite gel; Enrichment; Formalin-fixed and paraffin-embedded; Hydrophilic interaction liquid chromatography; Intact tryptic N-glycopeptide; Size exclusion chromatography.

MeSH terms

  • Acrylamide / chemistry*
  • Animals
  • Chromatography, Gel / methods*
  • Glycopeptides / analysis*
  • Glycopeptides / chemistry
  • Glycoproteins / chemistry
  • Glycosylation
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Mice
  • Proteolysis
  • Sepharose / chemistry*
  • Thymoma / chemistry*
  • Thymus Neoplasms / chemistry*
  • Trypsin / chemistry

Substances

  • Glycopeptides
  • Glycoproteins
  • Acrylamide
  • Sepharose
  • Trypsin