Hydrophobic mannosides act as accepters for trypanosome α-mannosyltransferases

A series of hydrophobic mannosides were synthesized and tested for their ability to act as acceptor substrates for mannosyltransferases in a Trypanosoma brucei cell-free system, The thiooctyl α-mannosides and octyl α-mannosides all accepted single mannose residues in a-linkage, as judged by thin layer chromatography of the products before and after jack bean α-mannosidase digestion. The mannosylation reactions were inhibited by amphomycin, suggesting that the immediate donor was dolicholphosphate-mannose (Dol-P-Man) in all cases, The transferred α-mannose residues were shown to be both (α1-2 and α1-6 linked by Aspergillus phoenicis α-mannosidase and acetolysis treatments, respectively, These data suggest that the compounds can act as acceptor substrates for the Dol-P-Man dependent (α1-2 and α1-6 mannosyltransferases of the GPI biosynthetic pathway and/or the dolichol-cycle of protein N-glycosylation, One of the compounds, Manα1-6Manα1-O-(CH2)7CH3, inhibited endogenous GPI biosynthesis in the cell-free system, suggesting that it could be a substrate for the trypanosome Dol-P-Man:Man2GlcN-PI α1-2 mannosyltransferase.