Matsusaki Michiya, Serizawa Takeshi, Kishida Akio, Akashi Mitsuru
Department of Molecular Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan.
Biomacromolecules. 2005 Jan-Feb;6(1):400-7. doi: 10.1021/bm049492o.
Basic fibroblast growth factor (FGF-2) mitogenic activities of sulfonated poly(gamma-glutamic acid) (gamma-PGA-S) were investigated with chlorate-treated L929 fibroblast culture tests. When 72% of the carboxyl groups in gamma-PGA were sulfonated (gamma-PGA-S72), cell numbers reached a maximum. The activity of gamma-PGA-S72 was higher than that of gamma-PGA and synthetic heparinoids and was almost comparable to that of heparin. Cytotoxicity of gamma-PGA-S72 was not observed, regardless of the degree of sulfonation. FGF-2-protective effects of gamma-PGA-S72 against acid and thermal inactivation were also evaluated, and gamma-PGA-S72 showed higher FGF-2-protective effects in comparison to nonsulfonated gamma-PGA. The steric structures of various sulfonated gamma-PGA-Ss were analyzed by molecular modeling (molecular orbital method (MOPAC)) and indicated that gamma-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 gamma-PGA-S and basic amino acid residues in FGF-2. gamma-PGA-S72 can interact with FGF-2 strongly.
通过氯酸盐处理的L929成纤维细胞培养试验，研究了磺化聚（γ-谷氨酸）（γ-PGA-S）的碱性成纤维细胞生长因子（FGF-2）促有丝分裂活性。当γ-PGA中72%的羧基被磺化时（γ-PGA-S72），细胞数量达到最大值。γ-PGA-S72的活性高于γ-PGA和合成类肝素，几乎与肝素相当。无论磺化程度如何，均未观察到γ-PGA-S72的细胞毒性。还评估了γ-PGA-S72对FGF-2的抗酸和抗热失活保护作用，与未磺化的γ-PGA相比，γ-PGA-S72显示出更高的FGF-2保护作用。通过分子建模（分子轨道法（MOPAC））分析了各种磺化γ-PGA-S的空间结构，结果表明γ-PGA-S在真空中呈螺旋状。MOPAC和分子力学方法（MM2）的结果表明，γ-PGA-S的磺酸基和羧基与FGF-2中的碱性氨基酸残基之间可发生静电相互作用。γ-PGA-S72能与FGF-2强烈相互作用。
