Chem2staB: a joint research chemistry laboratory for stabilization of membrane therapeutic targets
April 29, 2021
In 2016, CALIXAR and the University of Avignon (France) were glad to launch the Chem2staB laboratory (from CHEMistry to STABilization). This unique and joint laboratory was built to develop new molecules able to extract, stabilize and/or promote crystallization of therapeutic targets (membrane proteins, antigens, …) by preserving their entire integrity.
After 5 years of collaboration between chemists and biochemists from Avignon University (UMR 5247 - Bioorganic chemistry and amphiphilic systems - CBSA) and R&D CALIXAR’s team, a large variety of high potential products were identified. All the developed surfactants are useful to any life science projects involving membrane proteins. Among them, some are used especially to solubilize membrane proteins, other to stabilize membrane proteins before their purification steps. Lastly, a crystallization kit has been designed for drug discovery purposes.
The collaborative expertise led to identify several classes of relevant structures to answer membrane proteins handling:
Hydrogenated, fluorinated and hybrid detergents that can act as solubilizing and stabilizing agents (1)(2)(3)
Mild sugar-based detergents (2)(3)(4)
Small polymeric amphiphilic solubilizing and stabilizing compounds (5)
Non-ionic polymeric structures inspired by SMA (5)
By focusing our efforts on understanding and rationalization interactions between detergents and proteins, we have developed more accurate and innovative tools for biochemists interested in membrane proteins (6).
Several publications showed the high performances of these compounds. Last year, CALIXAR, Chem2staB and TU Technische Universität Kaiserslautern published a work in the European Journal of Organic Chemistry(7) that highlights the synthesis of three monomers which allowed solubilizing phospholipid vesicles and extract a broad range of membrane proteins.
Thanks to a strong dynamism of the laboratory, research is carried out continuously to provide new polymers allowing to work with more therapeutic targets. This development reinforces CALIXAR's expertise in using these compounds in industrial projects ordered by their customers, biotechnology and pharmaceutical companies.
(1) Pierre Guillet et al. Hydrogenated Diglucose Detergents for Membrane-Protein Extraction and Stabilization. Langmuir 2019, 35, 4287–4295. (2) Clarisse Faugier et al. Lactobionamide-based fluorinated detergent for functional and structural stabilization of membrane proteins. Methods 2020, 180, 19-26. (3) Gildas Nyame Mendendy Boussambe et al. Fluorinated diglucose detergents for membrane-protein extraction. Methods 2018, 147, 84-94. (4) Julien Dauvergne et al. Glycosylated Amphiphilic Calixarene‐Based Detergent for Functional Stabilization of Native Membrane Proteins. ChemistrySelect 2019, 4, 5535-5539. (5) Christophe Bonnet et al. Hybrid Double-Chain Maltose-Based Detergents: Synthesis and Colloidal and Biochemical Evaluation. The Journal of Organic Chemistry 2019, 84, 10606-10614. (6) Stéphane Abel et al. Structural insights into the membrane receptor ShuA in DDM micelles and in a model of gram-negative bacteria outer membrane as seen by SAXS and MD simulations. Biochimica et Biophysica Acta 2021, 1863, 2, 183504. (7) Christophe Bonnet et al. Detergent-Like Polymerizable Monomers : Synthesis, Physicochemical, and Biochemical Characterization. European Journal of Organic Chemistry 2020, 33, 5340-5349.