Synthesis of non-hydrolysable mimics of glycosylphosphatidylinositol (GPI) anchors

Org Biomol Chem. 2014 Feb 21;12(7):1163-72. doi: 10.1039/c3ob42116c.

Abstract

Synthesis of first generation non-hydrolysable C-phosphonate GPI analogs, viz., 6-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol-1-O-(sn-3,4-bis(palmitoyloxy)butyl-1-phosphonate) and 6-O-(2-amino-2-deoxy-α-d-glucopyranosyl)-d-myo-inositol-1-O-(sn-2,3-bis(palmitoyloxy)propyl-1-phosphonate) 23b, is reported. The target compounds were synthesized by the coupling of α-pseudodisaccharide 21 with phosphonic acids 18a and 18b respectively in quantitative yield followed by de-protection. These synthetic C-phosphonate GPI-probes were resistant to phosphatidylinositol specific phospholipase C (PI-PLC) and also showed moderate inhibition of the enzyme activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Glycosylphosphatidylinositols / chemical synthesis*
  • Glycosylphosphatidylinositols / chemistry
  • Glycosylphosphatidylinositols / pharmacology
  • Molecular Conformation
  • Structure-Activity Relationship
  • Type C Phospholipases / antagonists & inhibitors
  • Type C Phospholipases / metabolism

Substances

  • Enzyme Inhibitors
  • Glycosylphosphatidylinositols
  • Type C Phospholipases