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

Carbohydr Polym. 2015 Mar 6;117:400-407. doi: 10.1016/j.carbpol.2014.09.079. Epub 2014 Oct 7.


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.

Keywords: Chemically modified heparin; Glycol-split; IL-8; Inflammatory network; Neutrophil elastase; TNF-alpha.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anticoagulants / chemical synthesis
  • Anticoagulants / chemistry
  • Anticoagulants / pharmacology*
  • Dose-Response Relationship, Drug
  • Enzyme-Linked Immunosorbent Assay
  • Heparin / analogs & derivatives*
  • Heparin / chemical synthesis
  • Heparin / chemistry
  • Heparin / pharmacology*
  • Humans
  • Inflammation / drug therapy*
  • Inflammation / metabolism
  • Interleukin-8 / analysis
  • Leukocyte Elastase / antagonists & inhibitors
  • Leukocyte Elastase / metabolism
  • Proteinase Inhibitory Proteins, Secretory / chemical synthesis
  • Proteinase Inhibitory Proteins, Secretory / chemistry
  • Proteinase Inhibitory Proteins, Secretory / pharmacology*
  • Structure-Activity Relationship


  • Anticoagulants
  • Interleukin-8
  • Proteinase Inhibitory Proteins, Secretory
  • Heparin
  • Leukocyte Elastase