Biotechnological Engineering of Heparin/Heparan Sulphate: A Novel Area of Multi-Target Drug Discovery

Author(s): Marco Rusnati, Pasqua Oreste, Giorgio Zoppetti, Marco Presta

Journal Name: Current Pharmaceutical Design

Volume 11 , Issue 19 , 2005

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Heparin is a sulphated glycosaminoglycan currently used as an anticoagulant and antithrombotic drug. It consists largely of 2-O-sulphated IdoA → N, 6-O-disulphated GlcN disaccharide units. Other disaccharides containing unsulphated IdoA or GlcA and N-sulphated or N-acetylated GlcN are also present as minor components. This heterogeneity is more pronounced in heparan sulphate (HS), where the low-sulphated disaccharides are the most abundant. Heparin/HS bind to a variety of biologically active polypeptides, including enzymes, growth factors and cytokines, and viral proteins. This capacity can be exploited to design multi-target heparin/HS-derived drugs for pharmacological interventions in a variety of pathologic conditions besides coagulation and thrombosis, including neoplasia and viral infection. The capsular K5 polysaccharide from Escherichia coli has the same structure as the heparin precursor N-acetyl heparosan. The possibility of producing K5 polysaccharide derivatives by chemical and enzymatic modifications, thus generating heparin/HS-like compounds, has been demonstrated. These K5 polysaccharide derivatives are endowed with different biological properties, including anticoagulant/antithrombotic, antineoplastic, and anti-AIDS activities. Here, the literature data are discussed and the possible therapeutic implications for this novel class of multi-target “biotechnological heparin/HS” molecules are outlined.

Keywords: aids, angiogenesis, endothelium, fgf, heparin, tumour, coagulation

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Article Details

Year: 2005
Page: [2489 - 2499]
Pages: 11
DOI: 10.2174/1381612054367553
Price: $65

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