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dc.contributor.authorPye, David A
dc.contributor.authorKumar, Shant
dc.date.accessioned2010-02-23T13:18:13Z
dc.date.available2010-02-23T13:18:13Z
dc.date.issued1998-07-30
dc.identifier.citationEndothelial and fibroblast cell-derived heparan sulphate bind with differing affinity to basic fibroblast growth factor. 1998, 248 (3):889-95 Biochem. Biophys. Res. Commun.en
dc.identifier.issn0006-291X
dc.identifier.pmid9704022
dc.identifier.doi10.1006/bbrc.1998.9081
dc.identifier.urihttp://hdl.handle.net/10541/92756
dc.description.abstractHeparan sulphate from endothelial cells (ECHS) has been shown to bind to bFGF with a lower affinity than that seen for 3T3 fibroblast HS (FHS). To investigate the structural reasons for the low affinity binding of ECHS to bFGF, enzymatic degradation of intact ECHS and FHS chains was undertaken. Filter binding assays showed ECHS heparinase III-resistant fragments 6-7 disaccharides in length and had affinity for bFGF equivalent to that of the intact ECHS chains. The largest resistant fragments from FHS, again 6-7 disaccharides in length, bound to bFGF with a similar affinity to the largest ECHS oligosaccharides, and they therefore have considerably lower affinity than seen for the intact FHS chains. Disaccharide compositional analysis of both ECHS and FHS oligosaccharides showed them to contain similar amounts of 2-O-, 6-O-, and N-sulphated disaccharides. These results suggest that the sulphation pattern within sulphated HS domains and their overall length are not the sole contributors to the binding of intact HS chains to bFGF. It is suggested that domain organisation and frequency of occurrence of large heparinase III-resistant oligosaccharides within intact chains play an important role not only in governing the maximum observed binding affinity of intact chains in the assay system used, but also in the regulation of other biological properties of HS.
dc.language.isoenen
dc.subject.mesh3T3 Cells
dc.subject.meshAnimals
dc.subject.meshAorta
dc.subject.meshBinding Sites
dc.subject.meshCarbohydrate Sequence
dc.subject.meshCattle
dc.subject.meshCells, Cultured
dc.subject.meshDisaccharides
dc.subject.meshEndothelium, Vascular
dc.subject.meshFibroblast Growth Factor 2
dc.subject.meshFibroblasts
dc.subject.meshGlucosamine
dc.subject.meshHeparitin Sulfate
dc.subject.meshMice
dc.subject.meshMolecular Sequence Data
dc.subject.meshOligosaccharides
dc.titleEndothelial and fibroblast cell-derived heparan sulphate bind with differing affinity to basic fibroblast growth factor.en
dc.typeArticleen
dc.contributor.departmentCRC Department of Drug Development, Christie Hospital, Manchester, United Kingdom. DPye@picr.man.ac.uken
dc.identifier.journalBiochemical and Biophysical Research Communicationsen
html.description.abstractHeparan sulphate from endothelial cells (ECHS) has been shown to bind to bFGF with a lower affinity than that seen for 3T3 fibroblast HS (FHS). To investigate the structural reasons for the low affinity binding of ECHS to bFGF, enzymatic degradation of intact ECHS and FHS chains was undertaken. Filter binding assays showed ECHS heparinase III-resistant fragments 6-7 disaccharides in length and had affinity for bFGF equivalent to that of the intact ECHS chains. The largest resistant fragments from FHS, again 6-7 disaccharides in length, bound to bFGF with a similar affinity to the largest ECHS oligosaccharides, and they therefore have considerably lower affinity than seen for the intact FHS chains. Disaccharide compositional analysis of both ECHS and FHS oligosaccharides showed them to contain similar amounts of 2-O-, 6-O-, and N-sulphated disaccharides. These results suggest that the sulphation pattern within sulphated HS domains and their overall length are not the sole contributors to the binding of intact HS chains to bFGF. It is suggested that domain organisation and frequency of occurrence of large heparinase III-resistant oligosaccharides within intact chains play an important role not only in governing the maximum observed binding affinity of intact chains in the assay system used, but also in the regulation of other biological properties of HS.


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