Sébastien Ulrich “!Dynamic expression of multivalency in DNA

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
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