Show simple item record

dc.contributor.authorTurnbull, Jeremy E
dc.contributor.authorFernig, D G
dc.contributor.authorKe, Y
dc.contributor.authorWilkinson, M C
dc.contributor.authorGallagher, John T
dc.date.accessioned2010-08-03T11:33:11Z
dc.date.available2010-08-03T11:33:11Z
dc.date.issued1992-05-25
dc.identifier.citationIdentification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate. 1992, 267 (15):10337-41 J. Biol. Chem.en
dc.identifier.issn0021-9258
dc.identifier.pmid1587820
dc.identifier.urihttp://hdl.handle.net/10541/108943
dc.description.abstractThe structural properties of fibroblast heparan sulfate (HS) that are necessary for it to bind strongly to basic fibroblast growth factor (bFGF) have been investigated using bFGF affinity chromatography. Specific enzymic and chemical scission of HS, together with chemical N-desulfation, revealed that N-sulfate groups and iduronate-2-sulfates (IdoA(2-OSO3)) were essential for the interaction. bFGF-affinity chromatography of sulfated oligosaccharides released from HS by treatment with heparitinase led to the identification of an oligosaccharide component (oligo-H), seven disaccharides in length, with a similar affinity for bFGF as the parent molecule. Heparinase treatment of this fraction abolished the high affinity binding to bFGF. Analysis of oligo-H indicated that 74% of the disaccharide units had the structure IdoA(2-OSO3)alpha 1,4GlcNSO3; the remainder comprised N-acetylated and N-sulfated units, the majority of which were devoid of O-sulfate groups. Oligo-H was fully degraded to disaccharides by treatment with nitrous acid. These results indicate that the sequence of oligo-H is as shown below. delta GlcA beta 1,4GlcNSO3 alpha 1,4[IdoA(2-OSO3)alpha 1,4GlcNSO3]5 alpha 1, 4IdoA alpha 1,4GlcNAc Sulfated oligosaccharides of similar size but with a lower affinity for bFGF had a reduced concentration of IdoA(2-OSO3) but significant quantities of GlcNSO3(6-OSO3) and GlcNAc(6-OSO3). The data indicate a primary role for contiguous sequences of IdoA(2-OSO3)alpha 1,4GlcNSO3 in mediating the high affinity binding between fibroblast HS and bFGF.
dc.language.isoenen
dc.subject.meshBinding Sites
dc.subject.meshCarbohydrate Sequence
dc.subject.meshChromatography, Gel
dc.subject.meshChromatography, High Pressure Liquid
dc.subject.meshFibroblast Growth Factor 2
dc.subject.meshFibroblasts
dc.subject.meshHeparin Lyase
dc.subject.meshHeparitin Sulfate
dc.subject.meshHumans
dc.subject.meshMolecular Sequence Data
dc.subject.meshPolysaccharide-Lyases
dc.titleIdentification of the basic fibroblast growth factor binding sequence in fibroblast heparan sulfate.en
dc.typeArticleen
dc.contributor.departmentClinical Research Department, Christie Hospital, Manchester, United Kingdom.en
dc.identifier.journalJournal of Biological Chemistryen
html.description.abstractThe structural properties of fibroblast heparan sulfate (HS) that are necessary for it to bind strongly to basic fibroblast growth factor (bFGF) have been investigated using bFGF affinity chromatography. Specific enzymic and chemical scission of HS, together with chemical N-desulfation, revealed that N-sulfate groups and iduronate-2-sulfates (IdoA(2-OSO3)) were essential for the interaction. bFGF-affinity chromatography of sulfated oligosaccharides released from HS by treatment with heparitinase led to the identification of an oligosaccharide component (oligo-H), seven disaccharides in length, with a similar affinity for bFGF as the parent molecule. Heparinase treatment of this fraction abolished the high affinity binding to bFGF. Analysis of oligo-H indicated that 74% of the disaccharide units had the structure IdoA(2-OSO3)alpha 1,4GlcNSO3; the remainder comprised N-acetylated and N-sulfated units, the majority of which were devoid of O-sulfate groups. Oligo-H was fully degraded to disaccharides by treatment with nitrous acid. These results indicate that the sequence of oligo-H is as shown below. delta GlcA beta 1,4GlcNSO3 alpha 1,4[IdoA(2-OSO3)alpha 1,4GlcNSO3]5 alpha 1, 4IdoA alpha 1,4GlcNAc Sulfated oligosaccharides of similar size but with a lower affinity for bFGF had a reduced concentration of IdoA(2-OSO3) but significant quantities of GlcNSO3(6-OSO3) and GlcNAc(6-OSO3). The data indicate a primary role for contiguous sequences of IdoA(2-OSO3)alpha 1,4GlcNSO3 in mediating the high affinity binding between fibroblast HS and bFGF.


This item appears in the following Collection(s)

Show simple item record