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Mini-symposium Chimie IBMM

Chimie supramoléculaire et chimie des biomolecules : une interface fertile

Trois conférences par Jean-Louis Reymond, Gilles Guichard, Nicolas Giuseppone

publié le

Le Vendredi 02 décembre 2016 de 09h30 à 11h30
ENSCM, amphithéâtre de Forcrand (8 rue de l’école normale, Montpellier)

Programme :

1. Prof. Jean-Louis Reymond (Université de Berne, Suisse)
Chemical space discovery of bioactive small molecules and peptides

2. Dr. Gilles Guichard, DR CNRS (CBMN et IECB Institut Européen de Chimie et Biologie, UMR 5248 CNRS Université de Bordeaux, France)
Self-assembled foldamer nanostructures with confined space or inherent porosity

3. Prof. Nicolas Giuseppone (Université de Strasbourg | Institut Charles Sadron, CNRS UPR 22, France | membre IUF Institut Universitaire de France)
Integration of molecular motors in out-of-equilibrium polymer networks


Abstracts

1. Chemical space discovery of bioactive small molecules and peptides
Prof. Jean-Louis Reymond (Université de Berne, Suisse)

Chemical space describes the ensemble of all molecules that are possible by assembling atoms through covalent bonds. This concept is particularly relevant in drug discovery, where new molecular entities are constantly needed to develop new drugs addressing unmet medical needs. In our research we design cheminformatics methods for enumerating, mapping and virtual screening the chemical space of small organic molecules and peptides.[1, 2] We then implement these methods to choose, synthesize and test molecules in the laboratory. I will describe applications targeting ion channels,[3] transporters[4] and enzymes,[5] as well as new peptide based antibiotics against multi-drug resistant bacteria.[6]

References :
1. Reymond J-L. The Chemical Space Project. Acc. Chem. Res. 2015, 48, 722–730.
2. Jin X, Awale M, Zasso M, Kostro D, Patiny L, Reymond J-L Pdb-Explorer : a web-based interactive map of the protein data bank in shape space. BMC Bioinformatics 2015, 16, 339.
3. Simonin C, Awale M, Brand M, van Deursen R, Schwartz J, Fine M, Kovacs G, Häfliger P, Gyimesi G, Sithampari A, Charles R P, Hediger M, Reymond J-L. Optimization of Trpv6 calcium channel inhibitors using a new 3D ligand based virtual screening method. Angew. Chem., Int. Ed. 2015, 54, 14748–14752.
4. Montalbetti N, Simonin A, Simonin C, Awale M, Reymond J-L, Hediger M A. Discovery and characterization of a novel non-competitive inhibitor of the divalent metal transporter Dmt1/Slc11a2. Biochem. Pharmacol. 2015, 96, 216–224.
5. Kilchmann F, Marcaida M J, Kotak S, Schick T, Boss S D, Awale M, Gonczy P, Reymond J-L. Discovery of a selective Aurora A kinase inhibitor by virtual screening. J. Med. Chem. 2016, 59, 7188–7211.
6. Pires J, Siriwardena T N, Stach M, Tinguely R, Kasraian S, Luzzaro F, Leib S L, Darbre T, Reymond J-L, Endimiani A. In vitro activity of the novel antimicrobial peptide dendrimer G3kl against multidrug-resistant Acinetobacter Baumannii and Pseudomonas Aeruginosa. Antimicrob. Agents Chemother. 2015, 59, 7915–7918.

2. Self-assembled foldamer nanostructures with confined space or inherent porosity
Dr. Gilles Guichard, DR CNRS (CBMN et IECB Institut Européen de Chimie et Biologie, UMR 5248 CNRS Université de Bordeaux, France)

There is considerable interest in the development of peptides as self-assembling building units for use in a wide range of applications, including bio-sensing, catalysis, bio-materials and nano-materials.[1,2] Similarly, foldamers have a huge potential to fabricate both complex and atomically precise structures, with the added benefit of permitting the exploitation of a wider range of building units, thus enabling an increased divergence from nature.[3,4] However, the design of foldamers with the ability to self-assemble into defined nanostructures in aqueous conditions has proved exceptionally challenging. In this presentation, we will discuss some of our recent efforts towards this goal showing how de novo design and subsequent sequence manipulation of non peptide helical foldamers (aliphatic oligoureas[5]) in aqueous solutions may lead to the controllable [at least rationally explicable] formation of diverse protein-like higher-order structures such as compact and extended nanostructures.[6] Importantly, these assemblies present valuable structural features (i.e. isolated internal cavities and polar channels) which conceivably could lead to tailored functions.

References :
1. Hill R B, Raleigh D P, Lombardi A, DeGrado W F. De novo design of helical bundles as models for understanding protein folding and function. Acc. Chem. Res. 2000, 33, 745–754.
2. Bromley E H C, Channon K, Moutevelis E, Woolfson D N. Peptide and protein building blocks for synthetic biology : from programming biomolecules to self-organized biomolecular systems. ACS Chem. Biol. 2008, 3, 38–50.
3. Gellman S H. Foldamers : a manifesto. Acc. Chem. Res. 1998, 31, 173–180.
4. Guichard G, Huc I. Synthetic foldamers Chem. Commun. 2011, 47, 5933–5941.
5. Fischer L, Guichard G. Folding and self-assembly of aromatic and aliphatic urea oligomers : towards connecting structure and function. Org. Biomol. Chem. 2010, 8, 3101–3117.
6. Collie G W, Pulka-Ziach K, Lombardo C M, Fremaux J, Rosu F, Decossas M, Mauran L, Lambert O, Gabelica V, Mackereth C D, Guichard G. Shaping quaternary assemblies of water-soluble non-peptide helical foldamers by sequence manipulation Nat Chem. 2015, 7, 871–878.

3. Integration of molecular motors in out-of-equilibrium polymer networks
Prof. Nicolas Giuseppone (Université de Strasbourg | Institut Charles Sadron, CNRS UPR 22, France | membre IUF Institut Universitaire de France)

Making molecular machines that can be useful in the macroscopic world is a challenging long-term goal of nanoscience. Inspired by the protein machinery found in biological systems, and based on the theoretical understanding of the physics of motion at the nanoscale, organic chemists have developed a number of molecules that can produce work when triggered by various external chemical or physical stimuli. In particular, basic molecular switches that commute between at least two thermodynamic minima and more advanced molecular motors that behave as dissipative units working far from equilibrium when fueled with external energy have been reported. However, the ultimate challenge of coordinating individual molecular motors in a continuous mechanical process that can have a measurable effect at the macroscale has remained elusive until very recently. We will discuss advances developed by our group on artificial molecular machines and involving their mechanical coupling within dynamic polymeric systems. We will show that it is now possible to amplify their individual motions to achieve macroscopic functions in materials. In particular, we will present a dual-light controlled system operating fully out-of-equilibrium, and in which the integrated motions of two types of mechanically active units can be tuned by modulation of frequencies.

Contact local IBMM : Dr.Sébastien Ulrich (équipe Glycochimie)

Agenda

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