Novel functional biodegradable polymer II: fibroblast growth factor-2 activities of poly(gamma-glutamic acid)-sulfonate.
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.
Matsusaki
Michiya
M
Department of Molecular Chemistry, Graduate School of Engineering, Osaka University, 2-1 Yamada-oka, Suita 565-0871, Japan.
Serizawa
Takeshi
T
Kishida
Akio
A
Akashi
Mitsuru
M
D000818:Animals; D001673:Biodegradation, Environmental; D049109:Cell Proliferation / Q000187:drug effects; D016222:Fibroblast Growth Factor 2 / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008958:Models, Molecular; D011099:Polyglutamic Acid / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011108:Polymers / Q000737:chemistry*; D011489:Protein Denaturation / Q000187:drug effects; D013451:Sulfonic Acids / Q000138:chemical synthesis / Q000494:pharmacology*; D013696:Temperature; D013997:Time Factors
D011108:Polymers; D013451:Sulfonic Acids; D016222:Fibroblast Growth Factor 2; D011099:Polyglutamic Acid; D006493:Heparin