Further probing of the substrate specificities and inhibition of enzymes involved at an early stage of glycosylphosphatidylinositol (GPI) biosynthesis

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

Research output: Contribution to journalArticlepeer-review

18 Citations (Scopus)

Abstract

1-D-6-O-(2-Amino-2-deoxy-alpha-D-glucopyranosyl)-1-O-hexadecyl-myo-inositol (14), 1-D-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(octadecyl phosphate) (18), 1-D-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn- glycerol 3-phosphate) (24). 1-D-6-O-(2-amino-2-deoxy-alpha-D-mannopyranosyl)-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn- glycerol 3-phosphate) (30) and the corresponding 2-amino-2-deoxy-alpha-D-galactopyranosyl analogue 36 have been prepared and tested in cell-free assays as substrate analogues/inhibitors of alpha-(1-->4)-D-mannosyltransferases that are active early on in the glycosylphosphatidylinositol (GPI) biosynthetic pathways of Trypanosoma brucei and HeLa (human) cells. The corresponding N-acetyl derivatives of these compounds were similarly tested as candidate substrate analogues/inhibitors of the N-deacetylases present in both systems, Following on from an early study, 1-L-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-2-O-methyl-myo-inositol 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate) (44) was prepared and tested as an inhibitor of the trypanosomal alpha-(1-->4)-D-mannosyltransferase. A brief summary of the biological evaluation of the various analogues is provided. (C) 2002 Elsevier Science Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)2049-2059
Number of pages11
JournalCarbohyrdate Research
Volume337
Issue number21-23
Publication statusPublished - 19 Nov 2002

Keywords

  • glycosylphosphatidylinositol (GPI) membrane anchors
  • substrate analogues of 1-D-6-O-(2-amino-2-deoxy-alpha-D-glucopyranosyl)-myo-inositol
  • 1-(1,2-di-O-hexadecanoyl-sn-glycerol 3-phosphate)
  • GPI biosynthesis in Trypanosoma brucei and HeLa (human) cell-free systems
  • DE-N-ACETYLASE
  • PHOSPHATIDYLINOSITOL MEMBRANE ANCHORS
  • AFRICAN TRYPANOSOMES
  • D-GLUCOSAMINYLPHOSPHATIDYLINOSITOL
  • GLUCOSAMINYL PHOSPHATIDYLINOSITOL
  • ANALOGS
  • PATHWAY
  • PARASITE
  • CELLS
  • ACYLATION

Fingerprint

Dive into the research topics of 'Further probing of the substrate specificities and inhibition of enzymes involved at an early stage of glycosylphosphatidylinositol (GPI) biosynthesis'. Together they form a unique fingerprint.

Cite this