CALORIMETRIC STUDIES OF INTERACTIONS BETWEEN PROTEINS & VOLATILE ANESTHETICS

蛋白质之间相互作用的量热研究

• 批准号: 6122040
• 负责人: PAUL LIEBMAN
• 金额: --
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-08-05 至 1998-08-04
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6122040
• 关键词: anesthesiology; bioengineering /biomedical engineering; biological products; biomaterials; biomedical resource; education; genetics; human tissue; model design /development; technology /technique development

We are interested in the mechanism of action of volatile anesthetic agents such as halothane (2-bromo-2-chloro-1,1,1-trifluoroethane; molecular weight = 197.4; boiling point = 50.2C; specific gravity = 1.86 at 25 C; vapor pressure = 243 mm Hg at 20 C). While several investigators have shown significant effects of halothane on receptors and other systems of interest, we are taking a more fundamental approach and looking at the interaction between halothane and proteins on a molecular level. We want to understand the nature of the interaction, the energetics, and the stoichiometry. In experiments conducted to date, we have found that halothane increases the stability of bovine serum albumin (2 mg/ml, pH 7, 150 mM NaCl, 10 mM KPO4) in a concentration-dependent manner. The thermal transition midpoint is increased almost 10 C when halothane is dissolved to the maximum extent in aqueous medium (~ 19 mM). Such increased stability may prevent the dynamic structural changes that are normally required for protein function and may ultimately be the mechanism underlying volatile anesthetic action.

我们感兴趣的是挥发性的作用机制， 麻醉剂如氟烷 （2-溴-2-氯-1，1，1-三氟乙烷;分子量= 197.4; 沸点= 50.2 ℃;比重= 1.86（25 ℃）;蒸汽压 = 243 mm Hg（20 ℃）。 虽然一些调查人员已经表明， 氟烷对受体和其他系统的显著影响 兴趣，我们正在采取一种更根本的方法， 氟烷和蛋白质在分子水平上的相互作用。 我们 想要了解相互作用的本质，能量学， 化学计量 在迄今为止进行的实验中，我们发现 氟烷增加了牛血清白蛋白的稳定性（2 mg/ml，pH 7，150 mM NaCl，10 mM KPO4），浓度依赖性 方式 热转变中点增加了近10 ℃， 氟烷在水介质中的溶解度最大（~19 mM）。 这种增加的稳定性可以防止动态结构破坏。 蛋白质功能正常所需的变化， 最终成为挥发性麻醉剂的潜在机制 行动上