A Systematic Approach to the Chemical Synthesis of G-Protein Coupled Receptors

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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.