GPI anchor biosynthetic process
About - GPI biosynthesis disorders
Next to be assessed was the ability of GlcNR-PI analogues to inhibit MT-1 and/or later enzymes in the GPI pathway. This was achieved by pre-incubating the trypanosomal cell-free system with the analogues prior to incubation with GlcN-PI and GDP-[3H]Man. GlcNMal-PI and GlcPtu-PI showed little or no inhibition of the mannosylation of GlcN-PI when compared with the control (Figure , lanes 1, 3 and 7). GlcNBn-PI caused significant, but incomplete inhibition, whereas GlcNMe2-PI and Glc NCONH2-PI produced complete inhibition (Figure , lanes 4, 5 and 6). These inhibitory effects cannot be ascribed to non-specific effects, resulting from increased concentrations of synthetic lipid in the system, since pre-incubation with an equivalent concentration of GlcNAc-PI stimulated the biosynthetic pathway (Figure , lane 8).
Chapter 12 Inhibitors of GPI Biosynthesis - ScienceDirect
In this paper we describe the first mechanism-based suicide inhibitor of GPI biosynthesis, and combine features of this molecule with others to produce two parasite-specific suicide substrate inhibitors.