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J Biol Chem, Vol. 274, Issue 19, 13456-13461, May 7, 1999
§ and
From the The interaction of basic fibroblast growth
factor (bFGF) with heparan sulfate (HS)/heparin has been shown to
strongly enhance the activity of the growth factor although the
mechanism of activation is unclear. We have addressed the issue of the
minimal stoichiometry of an active HS oligosaccharide·bFGF complex by
chemically cross-linking the two components to form novel covalent
conjugates. The cross-linking procedure produced both monomeric and
dimeric bFGF·oligosaccharide complexes, which were purified to
homogeneity. Dimer conjugates were shown to have been formed as a
result of disulfide bridging of monomer conjugates. These monomer
conjugates were subsequently found to be biologically active in a
mitogenesis assay. We therefore conclude that a monomeric
bFGF·oligosaccharide complex is the minimal functional unit required
for mitogenic stimulation.
Cancer Research Campaign (CRC) Department of
Drug Development and Imaging and the § CRC and University of
Manchester Department of Medical Oncology, Paterson Institute for
Cancer Research, Christie Hospital,
Manchester M20 4BX, United Kingdom
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