Veraldi, N and Hughes, AJ and Rudd, TR and Thomas, HB and Edwards, SW and Hadfield, L and Skidmore, MA and Siligardi, G and Cosentino, C and Shute, JK and Naggi, A and Yates, EA (2015) Heparin derivatives for the targeting of multiple activities in the inflammatory response. Carbohydr Polym, 117. 400 - 407. ISSN 0144-8617

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Abstract

An attractive strategy for ameliorating symptoms arising from the multi-faceted processes of excessive and/or continual inflammation would be to identify compounds able to interfere with multiple effectors of inflammation. The well-tolerated pharmaceutical, heparin, is capable of acting through several proteins in the inflammatory cascade, but its use is prevented by strong anticoagulant activity. Derivatives of heparin involving the periodate cleavage of 2,3 vicinal diols in non-sulfated uronate residues (glycol-split) and replacement of N-sulphamido- with N-acetamido- groups in glucosamine residues, capable of inhibiting neutrophil elastase activity in vitro, while exhibiting attenuated anticoagulant properties, have been identified and characterised. These also interact with two other important modulators of the inflammatory response, IL-8 and TNF-alpha. It is therefore feasible in principle to modulate several activities, while minimising anticoagulant side effects, providing a platform from which improved anti-inflammatory agents might be developed.

Item Type: Article
Uncontrolled Keywords: Neutrophil elastase, IL-8, TNF-alpha, Inflammatory network, Chemically modified heparin, Glycol-split
Subjects: Q Science > Q Science (General)
Divisions: Faculty of Natural Sciences > School of Life Sciences
Related URLs:
Depositing User: Symplectic
Date Deposited: 25 Jan 2016 15:57
Last Modified: 31 May 2016 14:03
URI: http://eprints.keele.ac.uk/id/eprint/1414

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