Heparin, the widely used anticoagulant drug, is unusual among major pharmaceutical agents being neither single chemical entity nor a defined mixture of compounds. Its composition, while conforming to approximate average disaccharide composition or sulfation levels, exhibits heterogeneity and variability depending on the source, as well as its geographical origin. Furthermore, individual polysaccharide chains, whose physico-chemical properties are extremely similar, cannot be separated with current state-of-the-art techniques, presenting a challenge to those interested in the quality control of heparin, in ensuring its provenance and safety, and those with an interest in investigating the relationships between its structure and biological activity. The review consists of two main sections: The first is the Introduction, comprising (i) The History, Occurrence and Use of Heparin and (ii) Approaches to Structure-Activity Relationships. The second section is Improved Techniques for Structural Analysis, comprising; (i) Separation and Identification, (ii) Spectroscopic Methods, (iii) Enzymatic Approaches and (iv) Other Physico-Chemical Approaches. The ~60 references cover recent technological advances in the study of heparin structural analysis, largely since 2010.
Keywords: Heparin; Heparin provenance; Heparin regulation; Low molecular weight heparin; Structural analysis; Structure-activity.
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