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Article: Novel Chemical and Enzymatic Routes to the Generation of Heparin-related Polysaccharides

TitleNovel Chemical and Enzymatic Routes to the Generation of Heparin-related Polysaccharides
Authors
Keywords2-O-Sulphotransferase
Biosynthesis
Conjugation
Heparan Sulphate
Heparin
Neo-Glycosaminoglycan
Issue Date2000
Citation
Trends In Glycoscience And Glycotechnology, 2000, v. 12 n. 64, p. 121-127 How to Cite?
AbstractHeparin and heparan sulphate (HS) are characterised as a group of linear and highly sulphated polysaccharides of glycosaminoglycan (GAG) type. Heparin is produced mainly by connective tissue mast cells, whereas heparan sulfate is synthesized virtually by most cell types. Recently, interest is increasing in this group of polysaccharides due largely to its multiple biological functions and potential association with disease (1). In fact, heparin and HS have been implicated in modulating various biological processes, such as blood clotting, cell adhesion, growth factor signalling, and viral infection. The biological functions of heparin and HS largely depend on interactions of the negatively charged polysaccharide chain with a variety of proteins, such as proteases, protease inhibitors, growth factors, extracellular matrix components and viral proteins (2). In some cases, a single domain, generally consisting of less than 10 monosaccharide units but with a defined saccharide structure, is required for specific interaction with a selected protein. Moreover, the polysaccharide chain may form complexes with two or more proteins, identical or different. To induce biological response, these saccharide domains must be organized in a proper way. The enormous structural diversity of heparin/HS is created by a complex biosynthetic pathway (3). The biosynthesis of the polysaccharide chain is initiated by the formation of a precursor polymer composed of repeating disaccharide units of alternating D-glucuronic acid and N-acetyl-D-glucosamine, [-GlcA -GlcNAc-]n. While the chain is elongating, the polymer is modified by a series of sequential reactions including N-deacetylation/N-sulphation of GlcNAc, C5-epimerization of GlcA to L-iduronic acid (IdoA) and O-sulphation of IdoA at position C2 and of GlcN residues at position C6. In addition, to a lesser extent, O-sulphation of GIcA at position C2 and of GIcN at position C3 may also occur and appear to be biologically important. Most of the enzymes involved in HS biosynthesis have been characterised in molecular detail. Interestingly, some of these enzymes exist in several genetic isoforms with distinct substrate specificities (2, 4, 5).
Persistent Identifierhttp://hdl.handle.net/10722/179408
ISSN
2015 Impact Factor: 0.7
2015 SCImago Journal Rankings: 0.332
References

 

DC FieldValueLanguage
dc.contributor.authorRong, Jen_US
dc.date.accessioned2012-12-19T09:56:14Z-
dc.date.available2012-12-19T09:56:14Z-
dc.date.issued2000en_US
dc.identifier.citationTrends In Glycoscience And Glycotechnology, 2000, v. 12 n. 64, p. 121-127en_US
dc.identifier.issn0915-7352en_US
dc.identifier.urihttp://hdl.handle.net/10722/179408-
dc.description.abstractHeparin and heparan sulphate (HS) are characterised as a group of linear and highly sulphated polysaccharides of glycosaminoglycan (GAG) type. Heparin is produced mainly by connective tissue mast cells, whereas heparan sulfate is synthesized virtually by most cell types. Recently, interest is increasing in this group of polysaccharides due largely to its multiple biological functions and potential association with disease (1). In fact, heparin and HS have been implicated in modulating various biological processes, such as blood clotting, cell adhesion, growth factor signalling, and viral infection. The biological functions of heparin and HS largely depend on interactions of the negatively charged polysaccharide chain with a variety of proteins, such as proteases, protease inhibitors, growth factors, extracellular matrix components and viral proteins (2). In some cases, a single domain, generally consisting of less than 10 monosaccharide units but with a defined saccharide structure, is required for specific interaction with a selected protein. Moreover, the polysaccharide chain may form complexes with two or more proteins, identical or different. To induce biological response, these saccharide domains must be organized in a proper way. The enormous structural diversity of heparin/HS is created by a complex biosynthetic pathway (3). The biosynthesis of the polysaccharide chain is initiated by the formation of a precursor polymer composed of repeating disaccharide units of alternating D-glucuronic acid and N-acetyl-D-glucosamine, [-GlcA -GlcNAc-]n. While the chain is elongating, the polymer is modified by a series of sequential reactions including N-deacetylation/N-sulphation of GlcNAc, C5-epimerization of GlcA to L-iduronic acid (IdoA) and O-sulphation of IdoA at position C2 and of GlcN residues at position C6. In addition, to a lesser extent, O-sulphation of GIcA at position C2 and of GIcN at position C3 may also occur and appear to be biologically important. Most of the enzymes involved in HS biosynthesis have been characterised in molecular detail. Interestingly, some of these enzymes exist in several genetic isoforms with distinct substrate specificities (2, 4, 5).en_US
dc.languageengen_US
dc.relation.ispartofTrends in Glycoscience and Glycotechnologyen_US
dc.subject2-O-Sulphotransferaseen_US
dc.subjectBiosynthesisen_US
dc.subjectConjugationen_US
dc.subjectHeparan Sulphateen_US
dc.subjectHeparinen_US
dc.subjectNeo-Glycosaminoglycanen_US
dc.titleNovel Chemical and Enzymatic Routes to the Generation of Heparin-related Polysaccharidesen_US
dc.typeArticleen_US
dc.identifier.emailRong, J: jrong@hku.hken_US
dc.identifier.authorityRong, J=rp00515en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.scopuseid_2-s2.0-0034365372en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-0034365372&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume12en_US
dc.identifier.issue64en_US
dc.identifier.spage121en_US
dc.identifier.epage127en_US
dc.identifier.scopusauthoridRong, J=7005980047en_US

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