Chemo-enzymatic synthesis of the ALG1-CDG biomarker and evaluation of its immunogenicity

Bioorg Med Chem Lett. 2020 Dec 15;30(24):127614. doi: 10.1016/j.bmcl.2020.127614. Epub 2020 Oct 17.

Abstract

Congenital disorders of glycosylation (CDG) are a growing group diseases that result from defects in genes involved in glycan biosynthesis pathways. One tetrasaccharide, i.e., Neu5Ac-α2, 6-Gal-β1, 4-GlcNAc-β1, 4-GlcNAc, was recently reported as the biomarker of ALG1-CDG, the disease caused by ALG1 deficiency. To develop a novel diagnostic method for ALG1-CDG, chemo-enzymatic synthesis of the tetrasaccharide biomarker linked to phytanyl phosphate and the biomarker's immune stimulation were investigated in this study. The immunization study using liposomes bearing phytanyl-linked tetrasaccharide revealed that they stimulated a moderate immune response. The induced antibody showed strong binding specificity for the ALG1-CDG biomarker, indicating its potential in medical applications.

Keywords: ALG1-CDG; Biomarker; Congenital disorders of glycosylation; Immune response; Liposome; N-glycan.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies / analysis
  • Antibodies / immunology*
  • Antibody Formation*
  • Biomarkers / chemistry
  • Congenital Disorders of Glycosylation / diagnosis
  • Congenital Disorders of Glycosylation / immunology*
  • Diterpenes / administration & dosage
  • Diterpenes / chemistry
  • Diterpenes / immunology
  • Humans
  • Immunization
  • Mannosyltransferases / analysis
  • Mannosyltransferases / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Oligosaccharides / administration & dosage
  • Oligosaccharides / chemistry
  • Oligosaccharides / immunology*

Substances

  • Antibodies
  • Biomarkers
  • Diterpenes
  • Oligosaccharides
  • phytanol
  • Mannosyltransferases
  • chitobiosyldiphosphodolichol beta-mannosyltransferase