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

A Crossman, J S Brimacombe, M A J Ferguson, Terry K Smith

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

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. (C) 1999 Elsevier Science Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)42-51
Number of pages10
JournalCarbohyrdate Research
Volume321
Issue number1-2
Publication statusPublished - 15 Sept 1999

Keywords

  • glycosylphosphatidylinositol (GPI) membrane anchors
  • 1-D-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-2-O-octyl and-2-O-hexadecyl-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate)
  • 1-D-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(1,2-di-O-octyl-sn-glycerol 3-phosphate)
  • inhibition of GPI biosynthesis
  • GLUCOSAMINYL PHOSPHATIDYLINOSITOL
  • AFRICAN TRYPANOSOMES
  • PARASITE
  • SPECIFICITY
  • ACTIVATION
  • ACYLATION
  • CELLS

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