Chemical extension and glycodendrimer formation of the matriglycan decasaccharide, -(3Xylα1-3GlcAβ1)5- and its affinity for laminin

Carbohydr Res. 2025 Jan:547:109328. doi: 10.1016/j.carres.2024.109328. Epub 2024 Nov 22.

Abstract

Muscle tissue is stabilized by the strong interaction between laminin and matriglycan. Matriglycan is a polysaccharide composed of the repeating disaccharide, -3Xylα1-3GlcAβ1-, and is a pivotal part of the core M3 O-mannosyl glycan. Patients with muscular dystrophy cannot synthesize matriglycan or the core M3 O-mannosyl glycan due to a defect in or the lack of glycosyltransferases owing to glycan synthesis. Therefore, a supply of matriglycan may be a powerful tool for reconstructing muscle tissue in these patients. We herein report the synthesis of a matriglycan-repeating decasaccharide and a dendrimer comprising three branches of the decasaccharide. The glycan was regio- and stereoselectively synthesized by the stepwise addition of the corresponding disaccharide unit. The immobilized decasaccharide and glycodendrimer bound to laminin-G-like domains 4 and 5 of laminin-α2. The dissociation constants of the decasaccharide and dendrimer obtained from bio-layer interferometry were estimated to be 4.4 × 10-8 M and 6.8 × 10-8 M, respectively, showing higher affinity than those of a matriglycan-repeating hexasaccharide (1.6 × 10-7 M) and the dendrimer (1.8 × 10-7 M).

Keywords: Bio-layer interferometry; Core M3 O-Mannosyl glycan; Glycodendrimer; Laminin; Matriglycan.

MeSH terms

  • Carbohydrate Sequence
  • Dendrimers / chemistry
  • Humans
  • Laminin* / chemistry
  • Laminin* / metabolism
  • Oligosaccharides / chemical synthesis
  • Oligosaccharides / chemistry
  • Oligosaccharides / metabolism

Substances

  • Laminin
  • Oligosaccharides
  • Dendrimers