CONFORMATIONAL CONSEQUENCES OF A MEMBRANE ENVIRONMENT

膜环境的构象后果

• 批准号: 6188482
• 负责人: DALE F MIERKE
• 金额: $ 5.13万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-09-30 至 2002-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6188482
• 关键词: Raman spectrometry; artificial membranes; chemical hydration; circular dichroism; computer simulation; conformation; cooperative study; electron spin resonance spectroscopy; fluorescence spectrometry; infrared spectrometry; lipid bilayer membrane; membrane structure; micelles; molecular dynamics; nuclear magnetic resonance spectroscopy; peptide structure; synthetic peptide; vesicle /vacuole

In this grant application, a collaborative effort aimed at examining the conformational preferences of small peptides (as well as peptidomimetics) in the presence of small lipid vesicles, micelles, and reverse micelles is described. This research effort utilizes many spectroscopic techniques including nuclear magnetic resonance, circular dichroism, electron paramagetic resonance, fluorescence, infrared and Raman spectroscopy. For the refinement of the structures of the biomolecules, extensive computations will be carried out including molecular dynamics simulations, distance geometry-based calculations, and ab initio calculations for determination of the normal modes and principle stretching frequencies of the small peptides or peptidomimetics. From these studies the effects of the membrane environment, at differing levels of hydration, on the conformational preferences of small peptides and peptidomimetics will be ascertained. Considering that the receptor for many of these drug-candidates is membrane associated, this information is vital for the determination of the conformations first presented to the receptors during the initial binding process. In addition, reverse micelle-like environments have been utilized for delivery across membranes. Our results will shed insight into the structural preferences of the delivered material.

在此赠款应用中，描述了旨在研究在存在小脂质囊泡，胶束和反向胶束的情况下，旨在检查小肽（以及肽仪）的构象偏好的一项协作努力。 这项研究工作利用了许多光谱技术，包括核磁共振，循环二色性，电子超级吸引共振，荧光，红外和拉曼光谱。 为了改进生物分子的结构，将进行广泛的计算，包括分子动力学模拟，基于距离几何的计算以及确定小肽或肽匹配的正常模式和原理拉伸频率的临时计算。从这些研究中，将确定膜环境的影响，在不同水平的水平，对小肽和肽仪的构象偏好的影响。考虑到许多这些药物candi剂的受体与膜相关，因此该信息对于在初始结合过程中首先提交给受体的构象至关重要。 此外，已经使用了反向胶束样环境来跨膜递送。 我们的结果将洞悉交付材料的结构偏好。