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J Biol Chem, Vol. 274, Issue 30, 20953-20960, July 23, 1999

Structural Studies of N-Glycans of Filarial Parasites
CONSERVATION OF PHOSPHORYLCHOLINE-SUBSTITUTED GLYCANS AMONG SPECIES AND DISCOVERY OF NOVEL CHITO-OLIGOMERS

Stuart M. Haslam, Katrina M. Houston^§, William Harnett^§, Andrew J. Reason^¶, Howard R. Morris, and Anne Dell

From the  Department of Biochemistry, Imperial College, London SW7 2AY, the ^§ Department of Immunology, University of Strathclyde, Glasgow G4 0NR, and ^¶ M-Scan Ltd., Silwood Park, Sunninghill, Ascot SL5 7PZ, United Kingdom

N-Type glycans containing phosphorylcholine (PC-glycans), unusual structures found in the important human pathogens filarial nematodes, represent a novel target for chemotherapy. Previous work in our laboratories produced compositional information on the PC-glycan of ES-62, a secreted protein of the rodent parasite Acanthocheilonema viteae. In particular, we established using fast atom bombardment mass spectrometry (MS) analysis that PC was attached to a glycan with a trimannosyl core, with and without core fucosylation, carrying between one and four additional N-acetylglucosamine residues. In the present study, we demonstrate that this structure is conserved among filarial nematodes, including the parasite of humans, Onchocerca volvulus, for which new drugs are most urgently sought. Furthermore, by employing a variety of procedures, including collision-activated dissociation MS-MS analysis and matrix-assisted laser desorption MS analysis, we reveal that surprisingly, filarial nematodes also contain N-linked glycans, the antennae of which are composed of chito-oligomers. To our knowledge, this is the first report of such structures in a eukaryotic glycoprotein.

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Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

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