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.