Fibroblast growth factors, interaction with

One key NMR-based study has focused on the evaluation of the dynamic properties of heparin-like hexasaccharides.20 The analysis of Tj, T2 and NOE 13C-NMR data of biologically active synthetic compounds has shown that the sulphation pattern strongly influences the internal dynamics, and supports the importance of the GAGs flexibility on the selectivity of the interaction with fibroblast growth factors. 

Fromm, J.R., R.E. Hileman, E.E. Caldwell, J.M. Weiler, and R.J. Linhardt. 1995. Differences in the interaction of heparin with arginine and lysine and the importance of these basic amino acids in the binding of heparin to acidic fibroblast growth factor. Arch Biochem Biophys 323 279-287. 

S domains interact with both the fibroblast growth factor (FGF) and its receptor, bringing the oligomeric complex together and increasing the effectiveness of a low concentration of FGF. 

Faham S, Hileman RE, Fromm JR, Linhardt RJ, Rees DC, Heparin structure and interactions with basic fibroblast growth factor. Science I 996 271 (5252) I I I 6-1 120. 

The data for specificity are equally surprising. As shown in Table 20.1, an aptamer aimed at basic fibroblast growth factor (bFGF) does not bind tightly to other members of the FGF family or to other proteins known to interact with an acidic substance, heparin (these data were reported in [5]). Similar data exist for aptamers aimed at several reverse transcriptases, serine proteases, P- and L-selectin, and cytokines such as VEGF and PDGF. Aptamers in vitro show extreme specificity for their intended targets. 

Toledo MS, Suzuki E, Handa K, Hakomori S. Effect of ganglioside and tetraspanins in microdomains on interaction of in-tegrins with fibroblast growth factor receptor. J. Biol. Chem. 2005 280 16227-16234. 

Heparin has been used in enzyme purification such as recombinant human mast cell tryptase. The purified enzyme is fully active [12]. Heparin-based affinity chromatography also permitted the isolation of growth factors such as basic fibroblast growth factor (bFGF). The affinity is lower when bFGF is complexed with acidic gelatin [13]. The elution of synthetic TFPI (tissue factor pathway inhibitor) peptidic fragments on immobilized heparin has allowed one to find the peptidic sequence responsible for the TFPI-heparin interaction [14]. 

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