Chem2stab: Chemistry For Membrane Proteins

1.

mission

CHEM2STAB is a unique common research laboratory (LabCom) in the world by teaming up chemists and biochemists from Avignon University (UMR 5247 - Equipe Chimie Bioorganique et Systèmes Amphiphiles - CBSA) and from the start-up CALIXAR located in France (Lyon).

The main goal of CHEM2STAB is to develop new molecules able to extract, to stabilize and/or to promote crystallization of therapeutic targets or antigens (membrane proteins) without denaturing them. The research in the field of reagents for proteomic studies more precisely for the validation of pharmaceutical targets, is recent with major social and economic stakes in the field of human and animal health.

Actually, socio-economic studies (2011, Mark E Bunnage Nature Chemical Biology 7 « Getting pharmaceutical R&D back on target ») have highlighted the lack of innovation in the worldwide pharmaceutical industry and beyond the need to strengthen the research in the field of target/antigen validation in particular by using soft chemistry processes avoiding the foiling of the targets/antigens. Evidently, that greatly impacts the quality and performance of drugs and vaccines developed from this targets/ antigens.

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2.

activities

CHEM2STAB is structured through 4 activities areas:

- A first area concerns the research and the development of new detergents (in particular amphiphilic) able to extract i.e. solubilize all types of membrane proteins coming from different biological sources (cells bacteria, virus...).


- A second area develops the research in the field of surfactants for the stabilization of proteins (especially membrane proteins) before and after purification steps.


- The third area is dedicated to the biochemical validation of compounds developed through the areas 1 up to 2.


- The last area deals with the use and commercialization of compounds. CALIXAR will use directly the validated compounds on its industrial projects carried out with pharmaceutical or other biotech companies or with other life science academic groups or internally.

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3.

Publications

October 2020: 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

Abel, S.; Marchi, M.; Solier, J.; Finet, S.; Brillet, K.; Bonneté, F. Biochimica Et Biophysica Acta Bba - Biomembr (2021), 1863 (2), 183504. doi.org/10.1016/j.bbamem.2020.183504.

 

 

August 2020: DetergentLike Polymerizable Monomers: Synthesis, Physicochemical, and Biochemical Characterization

Here we report the synthesis of different monomers composed with a maltose polar head, an alkyl hydrogenated chain, and an acrylamide-based polymerizable moiety. These surfmers were able to solubilize phospholipid vesicles and to extract a broad range of proteins. 

Bonnet, C.; Guillet, P.; Mahler, F.; Igonet, S.; Keller, S.; Jawhari, A.; Durand, G. . Eur J Org Chem (2020) 33, 5340–5349. doi.org/10.1002/ejoc.202000540.

 

February 2020: Lactobionamide-based fluorinated detergent for functional and structural stabilization of membrane proteins

We report herein the use of a fluorinated lactobionamide-based detergent named FLAC6 for functional and structural stabilization of membrane proteins.    

C. Faugier, S. Igonet, D. Cornut, R. Besson, G. Durand, A. Jawhari, Methods. (2020). doi:10.1016/j.ymeth.2020.02.005.

August 2019: Hybrid Double-Chain Maltose-Based Detergents: Synthesis and Colloidal and Biochemical Evaluation

We report herein the synthesis of a new series of hybrid double-chain detergents presenting structural similarity with conventional and widely used n-alkyl maltoside detergents.

C. Bonnet, P. Guillet, S. Igonet, A. Meister, A. Marconnet, S. Keller, A. Jawhari, G. Durand, ,J. Org. Chem. (2019) 10606–10614. doi:10.1021/acs.joc.9b00873.

May 2019: Glycosylated Amphiphilic CalixareneBased Detergent for Functional Stabilization of Native Membrane Proteins

Here we report the synthesis and use of novel glycosylated amphiphilic calixarenebased detergent, named CALX173GK, for native membrane protein stabilization.

 J. Dauvergne, E.M. Desuzinges, C. Faugier, S. Igonet, M. Soulié, E. Grousson, D. Cornut, F. Bonneté, G. Durand, E. Dejean, A. Jawhari, Chem. Select (2019) 5535–5539. doi:10.1002/slct.201901220.

February 2019: Hydrogenated Diglucose Detergents for Membrane-Protein Extraction and Stabilization

We report herein the design and synthesis of a novel series of alkyl glycoside detergents consisting of a nonionic polar headgroup that comprises two glucose moieties in a branched arrangement (DG), onto which octane-, decane-, and dodecanethiols were grafted leading to ODG, DDG, and DDDG detergents, respectively.

P. Guillet, F. Mahler, K. Garnier, G.N.M. Boussambe, S. Igonet, C. Vargas, C. Ebel, M. Soulié, S. Keller, A. Jawhari, G. Durand, Langmuir (2019) 4287–4295. doi:10.1021/acs.langmuir.8b02842.

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4.

location

Avignon university

301 rue Baruch de Spinoza

BP 21239

84916 AVIGNON cedex 9

Calixar company

60 avenue ROCKEFELLER

69008 LYON

and

Bâtiment A 200 rue Michel de Montaigne

BP 21221

84911 AVIGNON

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5.

news

February 2020: Release of a new section « Publications »

Here you could find our latest publications

November 2019: Commercialization of new customized reagents (detergents/surfactants) for membrane protein isolation

Some references are commercially available off-the-shelf

September 2019: Starting of the Consolidation phase of the Labcom

Our labcom was recently granted with an additional funding from the ANR

April 2019: SMALP 2019 Conference

Last month, CHEM2STAB attended the SMALP meeting held in Utrecht. On this occasion we presented a poster on the use of novel maltose-based detergent for membrane protein solubilization. Very exciting talks and discussions all along this day of conference. Get ready for our new polymers to come! 

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6.

partners

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