Synthesis of a deuterated disaccharide internal standard for LC-MS/MS quantitation of heparan sulfate in biological samples

Carbohydr Res. 2024 Nov:545:109270. doi: 10.1016/j.carres.2024.109270. Epub 2024 Sep 7.

Abstract

High levels of heparan sulfate (HS) are a marker for several mucopolysaccharidosis (MPS) disorders which are lysosomal storage diseases caused by genetic defects in HS-degrading enzymes. Quantitation of HS in biological samples is therefore critical for diagnosis and evaluating the efficacy of new therapies. Herein we present the efficient synthesis of a butylated GlcN-GlcA disaccharide and its deuterated derivative for use as an internal standard in a quantitative mass spectrometry-based assay for analysis of HS following butanolysis. The synthesis features the stereoselective 1,2-cis glycosylation of a GlcA acceptor with a 6-O-benzoyl-2-deoxy-2-azido thioglucoside donor.

Keywords: Butanolysis; Disaccharide synthesis; Heparan sulfate; Mucopolysaccharidosis.

MeSH terms

  • Chromatography, Liquid
  • Deuterium / chemistry
  • Disaccharides* / chemical synthesis
  • Disaccharides* / chemistry
  • Heparitin Sulfate* / chemical synthesis
  • Heparitin Sulfate* / chemistry
  • Humans
  • Liquid Chromatography-Mass Spectrometry
  • Reference Standards
  • Tandem Mass Spectrometry*

Substances

  • Heparitin Sulfate
  • Disaccharides
  • Deuterium