Parasite glycoconjugates. Part 7.1 Synthesis of further substrate analogues of early intermediates in the biosynthetic pathway of glycosylphosphatidylinositol membrane anchors

Abstract

Substrate analogues of 1D-6-O-(2-amino-2-deoxy-α-D -glucopyranosyl)-myo-inositol 1-[sn-2,3-bis(myristoyloxy)propyl phosphate], an early intermediate in the biosynthesis of glycosylphosphatidylinositol (GPI) membrane anchors, have been prepared for biological evaluation with the α-(1→4)-D-mannosyltransferase of the protozoan parasite Trypanosoma brucei. The analogue α-D-GlcpNH₂-(1→6)-2- OMe-PI 2 is a substrate for the protozoan α-(1→4)-D-mannosyltransferase but not for the corresponding mammalian enzyme, whereas the analogues 3 and 4, in which the fatty-acid groups of the natural substrate are replaced by alkyl groups, are acceptable substrates for both the protozoan and mammalian enzymes.