Novel Functional Biodegradable Polymer II: Fibroblast Growth Factor-2 Activities of Poly(γ-glutamic acid)-sulfonate

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Abstract
Basic fibroblast growth factor (FGF-2) mitogenic activities of sulfonated poly(γ-glutamic acid) (γ-PGA-S) were investigated with chlorate-treated L929 fibroblast culture tests. When 72% of the carboxyl groups in γ-PGA were sulfonated (γ-PGA-S72), cell numbers reached a maximum. The activity of γ-PGA-S72 was higher than that of γ-PGA and synthetic heparinoids and was almost comparable to that of heparin. Cytotoxicity of γ-PGA-S72 was not observed, regardless of the degree of sulfonation. FGF-2-protective effects of γ-PGA-S72 against acid and thermal inactivation were also evaluated, and γ-PGA-S72 showed higher FGF-2-protective effects in comparison to nonsulfonated γ-PGA. The steric structures of various sulfonated γ-PGA-Ss were analyzed by molecular modeling (molecular orbital method (MOPAC)) and indicated that γ-PGA-Ss are helical in vacuo. Results from MOPAC and the molecular mechanics method (MM2) demonstrated that electrostatic interactions can take place between sulfonic and carboxyl groups of γ-PGA-S and basic amino acid residues in FGF-2. γ-PGA-S72 can interact with FGF-2 strongly.

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