Membrane proteins (MPs) are crucial cellular components, responsible for a range of key biological functions including inter- or intra-cellular material transfer and signal transduction and represent more than one-half of human drug targets. The high-resolution structures are essential to understand the underlying molecular mechanisms of these biomolecules and rational drug design efforts. Detergents are required to extract membrane proteins from the membranes and to maintain them in their native states in non-native environments. As conventional detergents have limited ability to stabilize membrane proteins, novel agents with enhanced efficacy need to be developed. Here we made efforts to develop stereoisomeric amphiphiles for membrane protein study and explore stereo-chemical outcome on stabilization of four different membrane proteins targeted here. Our collective efforts involving synthetic chemists, structural biologists and membrane protein scientists not only provide novel detergent tools useful for membrane protein study, but also include new detergent design guidelines for future development.
1. M. Das, Y. Du, J. S. Mortensen, O. Ribeiro, P. Hariharan, C. J. Loland, L. Guan, B. Byrne, B. K. Kobilka, P. S. Chae, Amphiphilic Stereoisomers for Membrane Protein Study: Importance of Chirality in the Hydrophobic Region. Chem. Sci., under review process.
2. M. Ehsan, Y. Du, N. J. Scull, E. Tikhonova, J. Tarrasch, J. S. Mortensen, C. J. Loland, G. Skiniotis, L. Guan, B. Byrne, B. K. Kobilka, P. S. Chae, Highly Branched Pentasaccharide-Bearing Amphiphiles for Membrane Protein Studies. J. Am. Chem. Soc. 2016, 138, 3789-3796.