Systematic Approach to the Chemical Synthesis (RMI)

化学合成的系统方法 (RMI)

• 批准号: 7014822
• 负责人: STEPHEN B.H. KENT
• 金额: $ 28.25万
• 依托单位: UNIVERSITY OF CHICAGO
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-09-23 至 2010-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7014822
• 关键词: cell surface receptors; membrane proteins; method development; peptide chemical synthesis; protein purification; protein structure; solubility

DESCRIPTION (provided by applicant): Polytopic helical integral membrane proteins are an important class of proteins that have been understudied because of technical issues regarding their expression, purification, and crystallization. Total chemical protein synthesis represents a potential route to these important proteins, but is currently hampered by insolubility of the transmembrane peptides required for protein assembly. To address this issue, we propose to develop a general method to render transmembrane peptides soluble for the manipulations necessary in chemical protein synthesis. We will then synthesize a 7 TM integral membrane protein to demonstrate the viability of chemical membrane protein synthesis. Establishing routine synthetic access to integral membrane proteins will provide tools to study their mechanisms in detail not currently available to molecular biology, which will eventually lead to a better understanding of how these proteins function in normal and pathological states.

描述（由申请人提供）：多位螺旋整合膜蛋白是一类重要的蛋白质，由于其表达、纯化和结晶方面的技术问题，其研究不足。总化学蛋白质合成代表了这些重要蛋白质的潜在途径，但目前受到蛋白质组装所需的跨膜肽的不溶性的阻碍。为了解决这个问题，我们建议开发一种通用的方法，使跨膜肽可溶于化学蛋白质合成中所需的操作。然后，我们将合成7 TM整合膜蛋白，以证明化学膜蛋白合成的可行性。建立常规的合成途径来获得完整的膜蛋白将提供工具来详细研究它们的机制，目前还没有分子生物学，这将最终导致更好地了解这些蛋白质在正常和病理状态下的功能。