Shah D, Johnston T P, Heitz S, Mitra A K
Division of Pharmaceutical Sciences, School of Pharmacy, University of Missouri-Kansas City, USA.
PDA J Pharm Sci Technol. 1998 Sep-Oct;52(5):209-14.
The purpose of this study was to determine the effects of various pharmaceutical additives on temperature and chaotrope-induced (guanidine HCl = GnHCl) denaturation of basic fibroblast growth factor (bFGF). The effect of various pharmaceutical additives on the stability (tertiary structure) of bFGF was assessed using fluoresence spectroscopy. An increase in the hydrophobicity of anionic surfactants (alkyl sulfonates) incubated with bFGF were shown to retard thermal-induced denaturation of bFGF. Increasing the concentration of decane sulfonate in an aqueous bFGF solution decreased the rate and extent of GnHCl-induced denaturation and demonstrated no inherent capacity to significantly alter the conformation of bFGF by itself. Structural differences in surfactants (e.g., aromatic, heterocyclics and straight-chain alkyl compounds) resulted in differences in the rate and extent of thermal-induced denaturation of bFGF. An increase in the concentration of citrate buffer increased the rate and extent of thermal-induced denaturation of bFGF. Results suggest that various excipients may affect the rate and extent of bFGF unfolding induced by chemical or thermal stress. Ionic charge and the degree of lipophilicity of an additive may significantly affect the rate and extent of the unfolding process.
本研究的目的是确定各种药用添加剂对碱性成纤维细胞生长因子（bFGF）温度诱导变性和离液剂诱导（盐酸胍=GnHCl）变性的影响。使用荧光光谱法评估各种药用添加剂对bFGF稳定性（三级结构）的影响。结果表明，与bFGF一起孵育的阴离子表面活性剂（烷基磺酸盐）疏水性增加会延缓bFGF的热诱导变性。在bFGF水溶液中增加癸烷磺酸盐的浓度会降低GnHCl诱导变性的速率和程度，并且其本身没有显著改变bFGF构象的内在能力。表面活性剂（如芳香族、杂环和直链烷基化合物）的结构差异导致bFGF热诱导变性的速率和程度存在差异。柠檬酸盐缓冲液浓度的增加会提高bFGF热诱导变性的速率和程度。结果表明，各种辅料可能会影响化学或热应激诱导的bFGF展开的速率和程度。添加剂的离子电荷和亲脂程度可能会显著影响展开过程的速率和程度。
