Synthesis of some second-generation substrate analogues of early intermediates in the biosynthetic pathway of glycosylphosphatidylinositol membrane anchors.
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.
Crossman
A
A
Department of Chemistry, University of Dundee, UK.
Brimacombe
J S
JS
Ferguson
M A
MA
Smith
T K
TK
D000818:Animals; D017261:Glycosylphosphatidylinositols / Q000096:biosynthesis / Q000138:chemical synthesis*; D006367:HeLa Cells; D006801:Humans; D007294:Inositol / Q000031:analogs & derivatives*; D008364:Mannosyltransferases / Q000037:antagonists & inhibitors; D015394:Molecular Structure; D014346:Trypanosoma brucei brucei
D017261:Glycosylphosphatidylinositols; D007294:Inositol; D008364:Mannosyltransferases