Nature of the Interaction of Heparin with Acidic Fibroblast Growth Factor

Henryk Mach, David B. Volkin, Carl J. Burke, C. Russell Middaugh, Robert J. Linhardt, Jonathan R. Fromm, Duraikkannu Loganathan, Lars Mattsson

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191 Scopus citations


The binding of human acidic fibroblast growth factor (aFGF) to heparin has been analyzed by a variety of different approaches to better elucidate the nature of this protein/sulfated polysaccharide interaction. Static and dynamic light scattering as well as analytical ultracentrifugation analyses indicates that 14–15 molecules of aFGF can bind to a 16-kDa heparin chain, with approximately 10 of these bound relatively uniformly to high-affinity sites. The dissociation constants of these latter sites are estimated to be approximately 50–140 nM on the basis of surface plasmon resonance experiments in which the association and dissociation rates of aFGF interaction with immobilized heparin were measured. The size of the binding site of aFGF on heparin was also determined by heparin lyase digestion of aFGF/heparin complexes followed by isolation and characterization of protected oligosaccharides. The smallest aFGF-protected oligosaccharide comigrated with ΔUA2S(l→4)-α-d-GlcNp2S6S(1→4)-α-l-IdoAp-2S(l→4)-α-dGlcNp2S6S (where ΔUA represents 4-deoxy-α-l-threo-hex-4-enopyranosyluronic acid and S is sulfate). Thus, aFGF appears to bind at high density (one molecule every 4–5 polysaccharide units) and with high affinity to heparin. This potentially provides a concentrated, stabilized storage form of the growth factor that can be released for receptor-mediated cellular activation in response to the proper stimuli. It is also possible that close proximity of aFGF molecules on the highly sulfated regions of heparan chains may be involved in the induction of receptor aggregation as suggested by Ornitz et al. [Ornitz, D. M., Yayon, A., Flanagan, J. G., Svahn, C. M., Levi, E., & Leder, P. (1992) Mol. Cell. Biol. 12, 240–247].

Original languageEnglish
Pages (from-to)5480-5489
Number of pages10
Issue number20
StatePublished - 1993
Externally publishedYes


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