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Heparin derivatives for the targeting of multiple activities in the inflammatory response

DOI: 10.1016/j.carbpol.2014.09.079 DOI Help
PMID: 25498652 PMID Help

Authors: Noemi Veraldi (Ronzoni Institute for Chemical and Biochemical Research) , Ashley J. Hughes (Diamond Light Source) , Timothy R. Rudd (Diamond Light Source) , Huw B. Thomas (University of Liverpool) , Steven W. Edwards (University of Liverpool) , Lynsay Hadfield (Keele University) , Mark Skidmore (University of Liverpool) , Giuliano Siligardi (Diamond Light Source) , Cesare Cosentino (Ronzoni Institute for Chemical and Biochemical Research) , Janis K. Shute (University of Portsmouth) , Annamaria Naggi (Ronzoni Institute for Chemical and Biochemical Research) , Edwin Yates (University of Liverpool)
Co-authored by industrial partner: No

Type: Journal Paper
Journal: Carbohydrate Polymers , VOL 117 , PAGES 400 - 407

State: Published (Approved)
Published: October 2014
Diamond Proposal Number(s): 8027

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.

Journal Keywords: Neutrophil Elastase; Il-8; Tnf-Alpha; Inflammatory Network; Chemically Modified Heparin; Glycol-Split

Subject Areas: Biology and Bio-materials, Medicine, Chemistry


Instruments: B23-Circular Dichroism

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