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Emmanuelle Thinon, 28 June 2017, 11 am, IECB Caroline Tokarski, 15 June 2017, 4pm, ENSCBP Christian Salesse, 8 June 2017, 4pm, ENSCBP Patrice Rey, 01 June 2017, 2h30 pm, ENSCBP Christina Sizun, 18 May 2017, 4 pm, ENSCBP Marisela Velez, 5 May 2017, 11am, IECB Iqbal Choudhary, 27 April 2017, 4 pm, ENSCBP Vincent Aucagne, 21 April 2017, 11 am, IECB Sophie Zinn-Justin, 14 April 2017, 11 am, IECB Cécile Feuillie, 16 February 2017, 4 PM, ENSCBP Félix M. Goñi, 8 december 2016, 4 pm, ENSCBP Félix M. Goñi, 17 november 2016, 4 pm, ENSCBP Carl Creutz, 20 october 2016, 4 pm, ENSCBP Diego Romero, 30 september 2016, 11 am, IECB A. Ciaccafava, 8 september 2016, 14h, ENSCBP A. Ramamoorthy, 16 June 2016, 16h, ENSCBP Alexandre de Brevern, 2 june 2016, ENSCBP Isabelle Landrieu, 26 May, 16h, ENSCBP Frances Sepavoric, 12 May, 16h, ENSCBP Thomas Pradeu, 7 April 2016, 9h, ENSCBP Françoise Argoul, 3 march 2016, 16h, ENSCBP Corinne Loutelier-Bourhis, 16/12/2015, 16h Aristotelis XENAKIS, 3 december 2015, 16h Fabian Kiessling, 26 november 2015, 11h Michaël Molinari, 20 november 2015, 11h Dipankar Das Sarma, 28 October 2015, 14h. Olivier Donard, 22 october 2015, 16h, ENSCBP E. Morvan & A.Grelard, 17/12/2015, 16h, ENSCBP Christophe Cullin, 10 september 2015, 14 h Brigitte Lindet, 18 June 2015, 16h, ENSCBP(B) Marion Decossas, 4 June 2015, 16h, ENSCBP(B) Pascale Schellenberger, 21 Mai 2015, 16h F. Leal-Calderon, 7 May 2015, 16h, ENSCBP(B) Ibrahim Abdulhalim, 9 April 2015, 14h, ENSCBP Manon Carré, 26 March 2015, 14h, ENSCBP(B) C. Bure & JM Schmitter, 19 March 2015, 16h T. Ogata & H. Ihara, 17 March 2015, 11h, IECB Banafshe Larijani, 12 March 2015, 16h, ENSCBP
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Emmanuelle Thinon, 28 June 2017, 11... Caroline Tokarski, 15 June 2017, 4p... Christian Salesse, 8 June 2017, 4pm... Patrice Rey, 01 June 2017, 2h30 pm,... Christina Sizun, 18 May 2017, 4 pm,... Marisela Velez, 5 May 2017, 11am, I... Iqbal Choudhary, 27 April 2017, 4 p... Vincent Aucagne, 21 April 2017, 11 ... Sophie Zinn-Justin, 14 April 2017, ... Cécile Feuillie, 16 February 2017,... Félix M. Goñi, 8 december 2016, 4... Félix M. Goñi, 17 november 2016, ... Carl Creutz, 20 october 2016, 4 pm,... Diego Romero, 30 september 2016, 11... A. Ciaccafava, 8 september 2016, 14... A. Ramamoorthy, 16 June 2016, 16h,... Alexandre de Brevern, 2 june 2016, ... Isabelle Landrieu, 26 May, 16h, ENS... Frances Sepavoric, 12 May, 16h, ENS... Thomas Pradeu, 7 April 2016, 9h, EN... Françoise Argoul, 3 march 2016, 1... Corinne Loutelier-Bourhis, 16/12/20... Aristotelis XENAKIS, 3 december 201... Fabian Kiessling, 26 november 2015,... Michaël Molinari, 20 november 2015... Dipankar Das Sarma, 28 October 2015... Olivier Donard, 22 october 2015, 16... E. Morvan & A.Grelard, 17/12/2015, ... Christophe Cullin, 10 september 201... Brigitte Lindet, 18 June 2015, 16h,... Marion Decossas, 4 June 2015, 16h, ... Pascale Schellenberger, 21 Mai 2015... F. Leal-Calderon, 7 May 2015, 16h, ... Ibrahim Abdulhalim, 9 April 2015, 1... Manon Carré, 26 March 2015, 14h, ... C. Bure & JM Schmitter, 19 March 20... T. Ogata & H. Ihara, 17 March 2015,... Banafshe Larijani, 12 March 2015, 1...
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Vincent Aucagne, 21 April 2017, 11 am, IECB

The seminar will take place, the 14th of April 2017, at 11 am, in the IECB amphitheatre, 2 rue Robert Escarpit Pessac.

 

 

Development of a molecular toolbox to simplify the chemical synthesis of proteins and constrained peptides natural products

 

 

Dr. Vincent Aucagne, Bioorthogonal & Synthetic Protein Chemistry group, Centre de Biophysique Moléculaire, Orléans

Email: vincent.aucagne@cnrs-orleans.fr

 

 

Abstract

 

The production of proteins by total synthesis is a very promising alternative to recombinant techniques for applications to the deciphering of biological mechanisms at the molecular level, drug discovery and synthetic biology. It is particularly useful for accessing site-specifically modified proteins or ones difficult to express.

 

Current technologies focus on the modular assembly of unprotected peptide fragments, through highly selective "chemical ligation" reactions. This approach revolutionized the field some thirty years ago and is gradually being democratized for the synthesis of small proteins (50-100 amino acids). However, access to more ambitious targets in terms of size or molecular complexity remains a real tour de force still reserved for rare specialists, at the cost of considerable efforts. Four major bottlenecks need to be overcome: (1) the assembly of multiple fragments by successive ligations, that requires repeated purification steps ultimately leading to very low overall yields, (2) the handling of poorly soluble or aggregation-prone fragments, and the development of more efficient ligation methods, from both the points of view of (3) the nature of the chemical reactions used and of (4) the synthesis of appropriately functionalized peptide fragments.

 

The main focus of my team relies on the chemistry-driven conception and development of original methodologies to overtake these limitations. Our ultimate goal is to build a robust and versatile molecular toolbox aimed at simplifying the access to medium-sized proteins, and thus offer to non-specialists widely applicable technologies. Our second major research axis is devoted to biology-driven applications, through the synthesis of disulfide-rich or other conformationally-constrained peptide natural products not accessible through standard peptide synthesis or recombinant techniques.

 

(1) V. Aucagne et al., Chem. Int. Ed. 2012, 51, 11320-11324; (2) M. T. Jacobsen et al., J. Am. Chem. Soc., 2016, 138, 11775−11782; (3) I. Valverde et al., Angew. Chem. Int. Ed. 2012, 51, 718-722; (4) V. P. Terrier et al., Chem. Sci., 2016, 7, 339−345.

 

Short CV

 

Vincent Aucagne received his PhD from the University of Orléans (2002), working on the development of synthetic methodologies to elaborate carbohydrate mimics such as C-glycosides and iminosugars. He was then hired as a fixed-term lecturer (ATER) to work on nucleoside analogs with antiviral properties (2002). Following post-doctoral research with Prof. David Leigh at the University of Edinburgh (2003-2006) in the field of mechanically-interlocked architectures and molecular machines, he returned to Orléans and joined the CNRS Center for Molecular Biophysics (CBM), as a CNRS Chargé de Recherche (2006) in the group of Dr Agnès Delmas. Since 2015, he leads the “Synthetic Proteins and Biorthogonal Chemistry” research group. His current research interests focuses on the development of synthetic methodologies to simplify the chemical synthesis of proteins, applications to the synthesis of biologically-relevant disulfide-rich miniproteins and development of peptide-based drugs.

 

Contact : Gilles Guichard g.guichard@iecb.u-bordeaux.fr

 

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