Pro-Membrane · Amphiphilic Peptoids as General Tool for Membrane Proteins Stabilization and Crystallization

Amphiphilic Peptoids as General Tool for Membrane Proteins Stabilization and Crystallization

"- What is the problem/issue being addressed? This action aimed to face the still unsolved challenge of stabilizing and crystallizing Membrane-Proteins (MPs). The innovative tool to reach this result is a particular class of amphiphilic peptoids. The intrinsically modular nature and the cell membrane permeability of peptoids, combined with a better understanding of their physical properties can establish the base of a general method for structural determination of MPs. - Why is it important for society? Membrane proteins (MPs) represent almost 60% of pharmaceutical targets. However, despite their fundamental role, only 2% of the protein of known structure are that of MPs, and, unfortunately, this lack of knowledge seriously affects structure-based drug design. While difficulties lay on overexpression, purification, stability and crystallization of MPs, the major bottleneck for their structural and functional study arises from their instability outside a lipid bilayer environment, where specific hydrophobic interactions keep the protein in its native and active conformational state. Therefore detergents that mimic the physical properties of the original bilayer are needed. Despite some success, currently available reagents did’nt open up the field, and a pressing need for new amphiphiles remains. - What are the overall objectives? A reiterative and comparative study of differently designed APOs libraries has been realized. In order to understand the macroscopic effects due to molecular changes, thermodynamic studies on the micellization process, and stabilization/crystallization screenings on model proteins was done and it's still an ongoing research through a strict collaboration between the partners and the two planned secondments of the researcher. Peptoids represent an endless source to “tune” the physical properties of micelles. These studies still need further investigations to reach the main objective, which is a a general and fast method to tune the aphipathic properties of the molecules ""on demand""."

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