Microbial heparin/heparan sulphate lyases: potential and applications |
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Authors: | C K M Tripathi Jaspreet Banga Vikas Mishra |
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Institution: | (1) Fermentation Technology Division, CSIR—Central Drug Research Institute, Post Box-173, Lucknow, Uttar Pradesh, 226001, India;(2) Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, 226014, India |
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Abstract: | Heparin/heparan sulphate glycosaminoglycans (HSGAGs) are composed of linear chains of 20–100 disaccharide units of N-acetylated d-glucosamine α (1–4) linked to glucuronic acid. HSGAGs are widely distributed on the cell surface and extracellular cell matrix
of virtually every mammalian cell type and play critical role in regulating numerous functions of blood vessel wall, blood
coagulation, inflammation response and cell differentiation. These glycosaminoglycans present in this extracellular environment
very significantly influence the blood coagulation system and cardiovascular functions. Recent studies have investigated the
mechanism by which cancer causes thrombosis and emphasizes the importance of the coagulation system in angiogenesis and tumour
metastasis. Heparan sulphate/heparin lyases or heparinases are a class of enzymes that are capable of specifically cleaving
the (1–4) glycosidic linkages in heparin and heparan sulphate to generate biologically active oligosaccharides with substantially
significant and distinct clinical, pharmaceutical and prophylactic/therapeutic applications. Bioavailability and pharmacokinetic
behaviour and characteristics of these oligosaccharides vary significantly depending on the origin/nature of the substrate
(heparin or heparan sulphate-like glycosaminoglycans), the source of enzyme and method of preparation. Various microorganisms
are reported/patented to produce these enzymes with different properties. Heparinases are commercially used for the depolymerization
of unfractionated heparin to produce low molecular weight heparins (LMWHs), an effective anticoagulant. Individual LMWHs are
chemically different and unique and thus cannot be interchanged therapeutically. Heparinases and LMWHs are reported to control
angiogenesis and metastasis also. This review catalogues the degradation of HSGAGs by microbial heparin/heparan sulphate lyases
and their potential either specific to the enzymes or with the dual role for generation of oligosaccharides for a new generation
of compounds, as shown by various laboratory or clinical studies. |
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