HYDROPHOBIC MANNOSIDES ACT AS ACCEPTORS FOR TRYPANOSOME ALPHA-MANNOSYLTRANSFERASES

A series of hydrophobic mannosides were synthesized and tested for the ir ability to act as acceptor substrates for mannosyltransferases in a Trypanosoma: brucei cell-free system. The thiooctyl alpha-mannosides and octyl alpha-mannosides all accepted single mannose residues in alp ha-linkage, as judged by thin layer chromatography of the products bef ore and after jack bean alpha-mannosidase digestion. The mannosylation reactions were inhibited by amphomycin, suggesting that the immediate donor was dolicholphosphate-mannose (Dol-P-Man) in all cases, The tra nsferred cu-mannose residues were shown to be both alpha 1-2 and alpha 1-6 linked by Aspergillus phoenicis alpha-mannosidase and acetolysis treatments, respectively. These data suggest that the compounds can ac t as acceptor substrates for the Dol-P-Man dependent alpha 1-2 and alp ha 1-6 mannosyltransferases of the GPI biosynthetic pathway and/or the dolichol-cycle of protein N-glycosylation. One of the compounds, Man alpha 1-6Man alpha 1-O-(CH2)(7)CH3, inhibited endogenous GPI biosynthe sis in the cell-free system, suggesting that it could be a substrate f or the trypanosome Dol-P-Man:Man(2)GlcN-PI alpha 1-2 mannosyltransfera se.