Hydrophobic mannosides act as acceptors for trypanosome alpha-mannosyltransferases

Glycobiology
J R BrownM A Ferguson

Abstract

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 alpha-mannosides and octyl alpha-mannosides all accepted single mannose residues in alpha-linkage, as judged by thin layer chromatography of the products before and after jack bean alpha-mannosidase digestion. The mannosylation reactions were inhibited by amphomycin, suggesting that the immediate donor was dolichol-phosphate-mannose (Dol-P-Man) in all cases. The transferred alpha-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 act as acceptor substrates for the Dol-P-Man dependent alpha 1-2 and alpha 1-6 mannosyltransferases of the GPI biosynthetic pathway and/or the dolichol-cycle of protein N-glycosylation. One of the compounds, Man alpha 1-6 Man alpha 1-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-Pl alpha 1-2 mannosyltransferase.

Citations

Jan 9, 1999·Trends in Neurosciences·J J Kim, K S Yoon
May 17, 2001·Bioorganic & Medicinal Chemistry·J R BrownD Chatterjec
Nov 26, 1999·Biochimica Et Biophysica Acta·M A FergusonT K Smith
Jun 12, 2010·Expert Opinion on Therapeutic Targets·Sunandini ChandraRam A Vishwakarma
Jul 28, 2017·Current Medicinal Chemistry·Ana Luísa Malaco MorottiIvone Carvalho
May 29, 2003·Biochimie·Cristiana Santos de MacedoNahid Azzouz

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