Systematic Approach to the Chemical Synthesis (RMI)

描述（由申请人提供）：多面体螺旋整体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，一直没有得到充分的研究。总化学蛋白合成是这些重要蛋白质的潜在途径，但目前由于蛋白质组装所需的跨膜肽的不溶解性而受到阻碍。为了解决这个问题，我们建议开发一种通用的方法，使跨膜肽在化学蛋白质合成中必要的操作中溶解。然后，我们将合成一个7 TM的完整膜蛋白，以证明化学膜蛋白合成的可行性。建立对整体膜蛋白的常规合成途径将为研究其分子生物学目前无法获得的详细机制提供工具，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。

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.