SUCRALFATE AND SOLUBLE SUCROSE OCTASULFATE BIND AND STABILIZE ACIDIC FIBROBLAST GROWTH-FACTOR

The actions of the anti-ulcer drug sucralfate have been proposed to be mediated through interaction with fibroblast growth factors (Folkman, J., Szabo, S., Strovroff, M., McNeil, P., Li, W. and Shing, Y. (1991) Ann. Surg. 214, 414-427). We show here that acidic fibroblast growth factor (aFGF; FGF-1) binds in vitro to both the soluble potassium salt and the insoluble aluminum salt of sucrose octasulfate, as demonstrat ed by a variety of biophysical techniques. Similar to the well-describ ed interaction and stabilization of aFGF by heparin, soluble sucrose o ctasulfate (SOS) stabilizes aFGF against thermal, urea and acidic pH-i nduced unfolding as determined by a combination of circular dichroism, fluorescence spectroscopy and differential scanning calorimetry. In a ddition, SOS also enhances the mitogenic activity of aFGF and partiall y protects the protein's three cysteine residues from copper-catalyzed oxidation. SOS competes with heparin and suramin for the aFGF polyani on binding site as measured by both fluorescence and light scattering based competitive binding assays. Front-face fluorescence measurements show that the native, folded form of aFGF binds to the insoluble alum inum salt of sucrose octasulfate (sucralfate). Moreover, sucralfate st abilizes aFGF against thermal and acidic pH-induced unfolding to the s ame extent as observed with SOS. Thus, due to their high charge densit y, SOS and sucralfate bind and stabilize aFGF via interaction with the aFGF polyanion binding site.