A versatile method for analysis of serine/threonine posttranslational modifications by β-elimination in the presence of pyrazolone analogues

Anal Chem. 2011 Dec 1;83(23):9060-7. doi: 10.1021/ac2019848. Epub 2011 Nov 1.

Abstract

Post-translational modifications (PTMs) of serine and threonine occur by diverse mechanisms, including phosphorylation, sulfation, and various types of sugar chain modifications, making characterization of the resulting structures very labor-intensive. Moreover, to fully understand the biological functions of PTMs, both the sites of modification and the modified structures must be analyzed. The present work describes a novel, versatile strategy in which the released O-glycan and the formerly glycosylated/phosphorylated peptide are labeled and thus amenable to further study. In this approach, glycopeptides/phosphopeptides are subjected to β-elimination in the presence of pyrazolone derivatives (BEP), which in the same reaction labels the formerly glycosylated/phosphorylated peptide. The reaction is essentially a β-elimination/Michael addition in which a carbon-carbon bond-forming Michael donor rather than a heteroatomic Michael donor is used. The O-glycans released upon BEP are recovered as bis-pyrazolone derivatives, without any detectable side reaction (peeling). Using this technique, the O-glycan profiles of model mucin-type glycoproteins were successfully analyzed. The BEP strategy discriminates between phosphorylated and GlcNAcylated peptides, since cleaved GlcNAc is detectable. In addition, both the released O-glycan and the formerly glycosylated peptide can be selectively labeled by different reagents via a β-elimination reaction performed in the presence of pyrazolone and the thiol Michael donor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glycopeptides / analysis
  • Phosphopeptides / analysis
  • Protein Processing, Post-Translational
  • Pyrazolones / chemistry*
  • Serine / chemistry*
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*
  • Threonine / chemistry*

Substances

  • Glycopeptides
  • Phosphopeptides
  • Pyrazolones
  • Threonine
  • pyrazolone
  • Serine