Hydrophobic mannosides act as accepters for trypanosome α-mannosyltransferases

Brown, Jillian R., Güther, Maria Lucia S., Field, Robert A. ORCID: https://orcid.org/0000-0001-8574-0275 and Ferguson, Michael A. J. (1997) Hydrophobic mannosides act as accepters for trypanosome α-mannosyltransferases. Glycobiology, 7 (4). pp. 549-558. ISSN 0959-6658

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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 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.

Item Type: Article
Additional Information: Funding Information: This work was supported by a program grant from The Wellcome Trust to M.A.J.F., a Wellcome Trust equipment grant to Prof. D. Gani, University of St. Andrews, and a Zeneca Strategic Research Fund grant to R.A.F. J.R.B. thanks The Chemicals and Pharmaceuticals Directorate of the Biotechnology and Biological Sciences Research Council for providing a research studentship. We thank Terry Smith, John Brimacombe, and Ravi Kartha for valuable discussions and advice and Trevor Rutherford for help with some of the NMR analyses. tvLAJJ. is a Howard Hughes Medical Institute International Research Scholar.
Uncontrolled Keywords: dolichol,glycosylphosphatidylinositol,mannosyltransferase,trypanosome,biochemistry ,/dk/atira/pure/subjectarea/asjc/1300/1303
Faculty \ School: Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
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Depositing User: LivePure Connector
Date Deposited: 11 Sep 2024 09:30
Last Modified: 25 Sep 2024 18:09
URI: https://ueaeprints.uea.ac.uk/id/eprint/96704
DOI: 10.1093/glycob/7.4.549

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