Off-line liquid chromatography-MALDI by with various matrices and tandem mass spectrometry for analysis of glycated human serum albumin tryptic peptides

Mol Nutr Food Res. 2007 Apr;51(4):456-61. doi: 10.1002/mnfr.200600291.

Abstract

Advanced glycation end-product (AGE)/peptides, arising from in vivo digestion of glycated proteins, are biologically important compounds, due to their reactivity against circulating and tissue proteins. For information on their possible structure, in vitro glycation of HSA and its further enzymatic digestion were performed. The resulting digestion product mixture was analysed directly by MALDI MS with various matrices [2,5-dihydroxy benzoic acid (DHB) and alpha-cyano-4-hydroxy cinnamic acid (CHCA)]. Alternatively, offline microbore LC prior to MALDI analysis was used, and showed that 63% of the free amino groups prone to glycation are modified, indicating the contemporary presence of unglycated peptides. This result proves that, regardless of the high glucose concentration employed for HSA incubation, glycation does not go to completion. Further studies showed that the collisionally activated decomposition of singly charged glycated peptides leads to specific fragmentation pathways, all related to the condensed glucose molecule. These unique product ions can be used as effective markers to establish the presence of a glucose molecule within a peptide ion.

MeSH terms

  • Glycated Serum Albumin
  • Glycation End Products, Advanced
  • Humans
  • Peptide Fragments / analysis*
  • Peptide Fragments / metabolism
  • Serum Albumin / chemistry*
  • Serum Albumin / metabolism
  • Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization*
  • Trypsin / metabolism*

Substances

  • Glycation End Products, Advanced
  • Peptide Fragments
  • Serum Albumin
  • Trypsin
  • Glycated Serum Albumin