Synthesis of some second-generation substrate analogues of early intermediates in the biosynthetic pathway of glycosylphosphatidylinositol membrane anchors

Carbohydr Res. 1999 Sep 15;321(1-2):42-51. doi: 10.1016/s0008-6215(99)00170-6.

Abstract

1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-2-O-octyl-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (23) and the corresponding 2-O-hexadecyl-D-myo-inositol compound 24 have been prepared as substrate analogues of an early intermediate in the biosynthetic pathway of glycosylphosphatidylinositol (GPI) membrane anchors. 1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(1,2-di-O-octyl-sn-glycerol 3-phosphate) has also been prepared as a substrate analogue. Biological evaluation of the analogues 23 and 24 revealed that they are neither substrates nor inhibitors of GPI biosynthetic enzymes in the human (HeLa) cell-free system but are potent inhibitors at different stages of GPI biosynthesis in the Trypanosoma brucei cell-free system.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glycosylphosphatidylinositols / biosynthesis
  • Glycosylphosphatidylinositols / chemical synthesis*
  • HeLa Cells
  • Humans
  • Inositol / analogs & derivatives*
  • Mannosyltransferases / antagonists & inhibitors
  • Molecular Structure
  • Trypanosoma brucei brucei

Substances

  • Glycosylphosphatidylinositols
  • Inositol
  • Mannosyltransferases