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Research

par Sebastien Ulrich - publié le , mis à jour le

SYNTHESIS OF CARBOHYDRATE ANALOGUES AND OLIGOSACCHARIDES. SYNTHESIS OF MULTIVALENT IMINOSUGARS

Coordinator : Prof. Alberto MARRA (alberto.marra enscm.fr)


DESIGN AND SYNTHESIS OF NANOPLATFORMS TARGETING THE CARBONIC ANHYDRASE IX INVOLVED IN CANCER

Coordinator : Prof. Jean-Yves WINUM (jean-yves.winum umontpellier.fr)


DYNAMIC & ADAPTIVE SYSTEMS FOR NUCLEIC ACIDS RECOGNITION AND DELIVERY

We develop dynamic multivalent recognition systems that self-assemble through dynamic covalent chemistry, adapt and respond to chemical stimuli. We specifically focus of achieving a functional control of the multivalent interactions with nucleic acids, which is crucial for applications as smart synthetic vectors in gene delivery. So far, we have reported on self-assembled peptide-based clusters (Fig. A), self-assembled metallo-organic clusters (Fig. B), and dynamic covalent polymers (Fig. C).

Key references :

  • Switching multivalent DNA complexation using metallo-controlled cationic supramolecular self-assemblies. W. Drożdż, Y. Bessin, V. Gervais, X.-Y. Cao, J.-M. Lehn, A. R. Stefankiewicz, S. Ulrich, Chem. Eur. J., 2018, 24 (7), 1518-1521. link
  • Bioactive clusters promoting cell penetration and nucleic acids complexation for drug and gene delivery applications : from designed to self-assembled and responsive systems. E. Bartolami, C. Bouillon, P. Dumy, S. Ulrich, Chem. Commun., 2016, 52, 4257-4273. link
  • Multivalent DNA recognition by self-assembled clusters : deciphering structural effects by fragments screening and evaluation as siRNA vectors. E. Bartolami, Y. Bessin, N. Bettache, M. Gary-Bobo, M. Garcia, P. Dumy, S. Ulrich, Org. Biomol. Chem., 2015, 13, 9427-9438. link
  • Dynamic expression of DNA complexation with self-assembled biomolecular clusters E. Bartolami, Y. Bessin, V. Gervais, P. Dumy, S. Ulrich, Angew. Chem. Int. Ed., 2015, 54 (35), 10183-10187. link
  • Degradable Hybrid Materials Based on Cationic Acylhydrazone Dynamic Covalent Polymers Promote DNA Complexation through Multivalent Interactions, C. Bouillon, D. Paolantoni, J. C. Rote, Y. Bessin, L. W. Peterson, P. Dumy, S. Ulrich, Chem. Eur. J., 2014, 20 (45), 14705-14714. link

Coordinator : Dr. Sébastien ULRICH (sebastien.ulrich enscm.fr)


SELF-ASSEMBLY OF BIOORGANIC ARCHITECTURES

We explore the self-fabrication of complex architectures by designing small organic (bio)molecules which combine through supramolecular and/or dynamic covalent linkages and generate novel and functional nanostructures. So far, we have reported on the design and one-pot self-selection of cages using multiple dynamic covalent reactions (Fig. D and E), and on the DNA-templated supramolecular self-assemblies of small molecule nano-arrays (Fig. F).

Key references :

  • Photomodulation of DNA-templated supramolecular assemblies. J. Rubio-Magnieto, T.-A. Phan, M. Fossépré, V. Matot, J. Knoops, T. Jarrosson, P. Dumy, F. Serein-Spirau, C. Niebel, S. Ulrich, M. Surin, Chem. Eur. J., 2018, 24 (3), 706-714. link
  • Generation of Multicomponent Molecular Cages using Simultaneous Dynamic Covalent Reactions. W. Drożdż, C. Bouillon, C. Kotras, S. Richeter, M. Barboiu, S. Clément, A. R. Stefankiewicz, S. Ulrich, Chem. Eur. J., 2017, 23, 18010-18018. link
  • One-Pot Self-Assembly of Peptide-Based Cage-Type Nanostructures using Orthogonal Ligations. E. Bartolami, J. Knoops, Y. Bessin, M. Fossépré, J. Chamieh, P. Dumy, M. Surin, S. Ulrich, Chem. Eur. J., 2017, 23, 14323-14331. link
  • A Dynamic Combinatorial Approach for Identifying Side Groups that Stabilize DNA-Templated Supramolecular Self-Assemblies, D. Paolantoni, S. Cantel, P. Dumy, S. Ulrich, Int. J. Mol. Sci., 2015, 16, 3609-3625 (special issue « Supramolecular interactions »). link
  • Probing the importance of π-stacking interactions in DNA-templated self-assembly of bisfunctionalized guanidinium compounds, D. Paolantoni, J. Rubio-Magnieto, S. Cantel, J. Martinez, P. Dumy, M. Surin, S. Ulrich, Chem. Commun., 2014, 50, 14257-14260. link

Coordinator : Dr. Sébastien ULRICH (sebastien.ulrich enscm.fr)


CHEMISTRY AND CHEMICAL-BIOLOGY FOR THE MODULATION OF EPIGENETIC MECHANISMS

The aim of this research is to identifiy new epigenetic modulators. it consists of several axis :

  • identification of new non-nucleoside DNA methyltransferase inhibitors, including glycosidic analogues
  • synthesis and biological evaluation of multivalent epigenetic inhibitors targeting DNA methyltransferases and histone deacetylases
  • synthesis of chemical probes and application of affinity-based protein profiling in cancer cell lines

The application fields of this research are :

  • anticancer therapies
  • anti-infectious strategy
  • comprehension of epigenetic mechanisms in pathological contexts

Coordinator : Dr. Marie LOPEZ (marie.lopez cnrs.fr)