By-Products of Heparin Production Provide a Diverse Source of Heparin-like and Heparan Sulfate Glycosaminoglycans.

Taylor, Sarah L ORCID: 0000-0002-6807-8627, Hogwood, John, Guo, Wei, Yates, Edwin A ORCID: 0000-0001-9365-5433 and Turnbull, Jeremy E ORCID: 0000-0002-1791-754X (2019) By-Products of Heparin Production Provide a Diverse Source of Heparin-like and Heparan Sulfate Glycosaminoglycans. Scientific reports, 9 (1). p. 2679.

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Abstract

Global production of pharmaceutical heparin (Hp) is increasing, and the production process from raw mucosal material results in large amounts of waste by-products. These contain lower sulfated Hp-like and heparan sulfate (HS), as well as other glycosaminoglycans, which are bioactive entities with pharmaceutical potential. Here we describe the first purification, structural and functional characterisation of Hp-like and HS polysaccharides from the four major by-product fractions of standard heparin production. Analysis of the by-products by disaccharide composition analysis and NMR demonstrated a range of structural characteristics which differentiate them from Hp (particularly reduced sulfation and sulfated disaccharide content), and that they are each distinct. Functional properties of the purified by-products varied, each displaying distinct anticoagulant profiles in different assays, and all exhibiting significantly lower global and specific inhibition of the coagulation pathway than Hp. The by-products retained the ability to promote cell proliferation via fibroblast growth factor receptor signalling, with only minor differences between them. These collective analyses indicate that they represent an untapped and economical source of structurally-diverse Hp-like and HS polysaccharides with the potential for enhancing future structure-activity studies and uncovering new biomedical applications of these important natural products.

Item Type:	Article
Uncontrolled Keywords:	Cell Line, Animals, Humans, Mice, Glycosaminoglycans, Heparin, Heparitin Sulfate, Disaccharides, Receptors, Fibroblast Growth Factor, Anticoagulants, Magnetic Resonance Spectroscopy, Technology, Pharmaceutical, Signal Transduction, Cell Proliferation, Blood Coagulation
Depositing User:	Symplectic Admin
Date Deposited:	06 Mar 2019 10:15
Last Modified:	19 Jan 2023 00:57
DOI:	10.1038/s41598-019-39093-6
Open Access URL:	https://doi.org/10.1038/s41598-019-39093-6
Related URLs:	Author Publisher
URI:	https://livrepository.liverpool.ac.uk/id/eprint/3033847