CE07 - Chimie moléculaire

Charge-Transfer Templated Ligation of DNA and Peptide Bioconjugates – CHAMELEON

Submission summary

Nature evolved to induce spatial confinement of biomolecules in order to regulate biological functions. Inspired by these natural processes scientists have artificially reproduced effective molarity-driven strategies to control molecular encountering and promote effective templated assemblies. To date the reported chemical strategies to assemble two biomolecules by increasing the effective molarity include DNA-, Antibody- or streptavidine-templated assemblies. However, these strategies are not devoid of limitations.
The goal of the CHAMELEON project is to develop an innovative, traceless and more importantly universal, templated ligation strategy that proceeds at low concentration under aqueous conditions for the generation of DNA-DNA, peptide-DNA and peptide-peptide constructs. Our strategy is built on electrostatic complementarity (charge-transfer) interactions between the electron-rich dialkoxynaphthalene (DAN) donor and the electron deficient naphthalene-tetracarboxylic diimide (NDI) acceptor units. Partner 1 recently described the synthesis and supramolecular assembly of new water-soluble poly(DAN/NDI) moieties linked by negatively charged phosphodiesters. Based on this expertise, we will take advantage of these tags respectively linked covalently via a cleavable linker to biomolecules (DNA or peptide) adequately functionalized by a reacting group to induce templated ligations in aqueous media.
The CHAMELEON project relies on the strong complementarity between ChemBioNAC and “Amino Acids, Peptides and Proteins” teams of the Institute of Biomolecules Max Mousseron in Montpellier. Both are strongly recognized in their respective fields and possess all the conceptual and technological know-how necessary to achieve the proposed goals of the project.
Realization of the CHAMELEON project will open new avenues for the construction of complex bioconjugates at low concentration with high specificity in aqueous media.

Project coordination

François MORVAN (Centre national de la recherche scientifique)

The author of this summary is the project coordinator, who is responsible for the content of this summary. The ANR declines any responsibility as for its contents.

Partner

IBMM Centre national de la recherche scientifique
IBMM Centre national de la recherche scientifique

Help of the ANR 364,538 euros
Beginning and duration of the scientific project: January 2023 - 42 Months

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