Sébastien Ulrich Our research interests focus on the dynamic expression of multivalency for the recognition and transport of biomolecules, in particular for gene delivery applications where “smart” dynamic materials able to complex therapeutic oligonucleotides in a controlled fashion are very much needed. Indeed, dynamic materials that selfassemble to express a multivalent binding of oligonucleotides and degrade in a controlled fashion to release their payload have gained a strong interest as “smart” transfection agents. We generate self-assembled materials using dynamic covalent chemistry such as chemoselective acylhydrazone and oxime bond formation.[2] Thus, we successfully prepared hybrid dynamic covalent polymers combining cationic and polyethylene oxide building blocks and demonstrated by HPLC analyses, fluorescence displacement assay and gel electrophoresis, that these systems are 1) degradable in a pHdependent manner (stable at neutral pH, undergo slow dissociation at pH 5.0), and 2) capable of effectively complexing dsDNA through multivalent interactions, even in biological serum, at N/P ratios comparable to PEI polymers (see figure). The main-chain self-assembly of dynamic covalent polymers through the incorporation of a pH-sensitive reversible covalent bond is therefore a promising strategy for generating degradable materials that are capable of establishing multivalent interactions and effectively complex dsDNA in biological media. More recently we expanded this approach to the template-assembled self-assembly of peptide-based clusters. In this context, we will show that the in situ generation of multivalency through programmed self-assembly based on dynamic covalent chemistry enables for the expression of DNA complexation and its control through ligand exchange. Chargé de Recherche CNRS Institut des Biomolécules Max Mousseron (IBMM), UMR 5247, Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM), Glycochemistry and Molecular Recognition team “!Dynamic expression of multivalency in DNA recognition” Vendredi 06 Mars, 11h à 12h Salle de Séminaires Bât. Recherche-Chimie, Faculté des Sciences Campus Valrose 28 Av. Valrose, Nice
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