Improved in-gel reductive β-elimination for comprehensive O-linked and sulfo-glycomics by mass spectrometry

J Vis Exp. 2014 Nov 20:(93):e51840. doi: 10.3791/51840.

Abstract

Separation of proteins by SDS-PAGE followed by in-gel proteolytic digestion of resolved protein bands has produced high-resolution proteomic analysis of biological samples. Similar approaches, that would allow in-depth analysis of the glycans carried by glycoproteins resolved by SDS-PAGE, require special considerations in order to maximize recovery and sensitivity when using mass spectrometry (MS) as the detection method. A major hurdle to be overcome in achieving high-quality data is the removal of gel-derived contaminants that interfere with MS analysis. The sample workflow presented here is robust, efficient, and eliminates the need for in-line HPLC clean-up prior to MS. Gel pieces containing target proteins are washed in acetonitrile, water, and ethyl acetate to remove contaminants, including polymeric acrylamide fragments. O-linked glycans are released from target proteins by in-gel reductive β-elimination and recovered through robust, simple clean-up procedures. An advantage of this workflow is that it improves sensitivity for detecting and characterizing sulfated glycans. These procedures produce an efficient separation of sulfated permethylated glycans from non-sulfated (sialylated and neutral) permethylated glycans by a rapid phase-partition prior to MS analysis, and thereby enhance glycomic and sulfoglycomic analyses of glycoproteins resolved by SDS-PAGE.

Publication types

  • Research Support, N.I.H., Extramural
  • Video-Audio Media

MeSH terms

  • Cations / chemistry
  • Chromatography, Ion Exchange / methods
  • Electrophoresis, Polyacrylamide Gel / methods
  • Glycomics / methods
  • Glycoproteins / analysis*
  • Humans
  • Mass Spectrometry / methods*
  • Mucins / analysis
  • Polysaccharides / analysis*
  • Proteomics / methods
  • Saliva / chemistry
  • Sulfates / analysis

Substances

  • Cations
  • Glycoproteins
  • Mucins
  • Polysaccharides
  • Sulfates