Mini review: structure and function of nematode phosphorylcholine-containing glycoconjugates

Buitrago, G., Duncombe-Moore, J., Harnett, M. M. and Harnett, W. (2021) Mini review: structure and function of nematode phosphorylcholine-containing glycoconjugates. Frontiers in Tropical Diseases, 2, 769000. (doi: 10.3389/fitd.2021.769000)

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Abstract

An unusual aspect of the biology of nematodes is the covalent attachment of phosphorylcholine (PC) to carbohydrate in glycoconjugates. Investigation of the structure of these molecules by ever-increasingly sophisticated analytical procedures has revealed that PC is generally in phosphodiester linkage with C6 of N-acetylglucosamine (GlcNAc) in both N-type glycans and glycosphingolipids. Up to five PC groups have been detected in the former, being located on both antenna and core GlcNAc. The PC donor for transfer to carbohydrate appears to be phosphatidylcholine but the enzyme responsible for transfer remains to be identified. Work primarily involving the PC-containing Acanthocheilonema viteae secreted product ES-62, has shown that the PC attached to nematode N-glycans possesses a range of immunomodulatory properties, subverting for example, pro-inflammatory signalling in various immune system cell-types including lymphocytes, mast cells, dendritic cells and macrophages. This has led to the generation of PC-based ES-62 small molecule analogues (SMAs), which mirror the parent molecule in preventing the initiation or progression of disease in mouse models of a number of human conditions associated with aberrant inflammatory responses. These include rheumatoid arthritis, systemic lupus erythematosus and lung and skin allergy such that the SMAs are considered to have widespread therapeutic potential.

Item Type:Articles
Keywords:Anti-inflammatory drug development, ES-62, glycoconjugate, immunomodulation, nematode, phosphorylcholine.
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Duncombe-Moore, Ms Josephine and Harnett, Professor Margaret and Buitrago, Dr Geraldine and Harnett, Professor William
Authors: Buitrago, G., Duncombe-Moore, J., Harnett, M. M., and Harnett, W.
College/School:College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation
Journal Name:Frontiers in Tropical Diseases
Publisher:Frontiers Media
ISSN:2673-7515
ISSN (Online):2673-7515
Copyright Holders:Copyright © 2021 Buitrago, Duncombe-Moore, Harnett and Harnett
First Published:First published in Frontiers in Tropical Diseases 2: 769000
Publisher Policy:Reproduced under a Creative Commons License

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