CE06 - Polymères, composites, physique et chimie de la matière molle

Survival of reactive systems for driving property-directed molecular evolution – SACERDOTAL

Submission summary

To endow molecules and materials with properties, chemists can rely on established structure-property relationships. This approach is relevant at the molecular and supramolecular levels, where much information exists for synthesis and prediction of physicochemical properties. In contrast, it is not enough mature to engineer complex functions integrating multiple interactions and reactions. As an alternative, a reverse property-to-structure strategy can be adopted by screening libraries of interacting/reacting components for targeted properties. However screening is time-consuming, which has limited the size of the libraries and thus the system diversity. Biologists do not experience this limit. Evolving living cells submitted to reproductive fitness, they couple cell survival with the property that they want to evolve. This powerful strategy is currently unprecedented in an abiotic system, which has motivated the SACERDOTAL project. Its goal is to introduce and validate, in a chemical monomers/polymers system, a selection/survival protocol for property-directed evolution.
Our protocol relies on a temperature gradient applied on a set of monomers engaged in reversible ligation/hydrolysis reactions. By sustaining an out-of-equilibrium state, it continuously forces the system to randomly explore the possible lengths and sequences of the polymers. Among the resulting library of myriads of polymers, the selection and the survival of a subpopulation is conditioned to the realization of the property sought for by tuning the experimental constraints. We adopted amino-acids and peptides as relevant monomers and polymers respectively since these compounds have found wide use to produce water-soluble nanoparticles for biomedical applications. Hence, we propose to select and produce peptide-conjugated nanoparticles by means of a survival assay that selects peptides for their abilities of binding at the nanoparticle surfaces and for their propensity to generate bright luminescent conjugates. This goal is significant for imaging since such nanoparticles still suffer from drawbacks (e.g. toxicity, lack of brightness and/or colloidal stability), which could be addressed by designing optimized protective shells surrounding the inorganic cores.
Thus this integrative and multidisciplinary project includes original chemical developments (dynamic combinatorial libraries of amino-acids, protocols for nanoparticle syntheses), theoretical and numerical simulations of non-equilibrium polymerization systems (from reaction-diffusion models to stochastic metadynamic models), design and implementation of instrumental set-ups (microdevices, optical heating and fluorescence imaging), and analyses of the peptide-conjugated nanoparticles and of their peptides by a battery of established or innovative techniques.
Beyond the production of functionalized nanoparticles, the validation of our selection/survival protocol for property-directed evolution will be also significant in a methodological perspective and be correspondingly patented for technology transfer and economic development. Our protocol addresses theoretical, instrumental, analytical issues, which should be common to all works in this emerging field. It exploits discriminative criteria (diffusion coefficients and rate constants of reactions), which overcome the thermodynamic ones used in most current screening protocols. It is compatible with numerous chemistries with a molecular diversity potentially exceeding the one presently accessible using microorganisms while being free from any physiological/toxicity constraints. In SACERDOTAL, it exploits libraries of peptides, which can exhibit multiple types of interactions and catalytic properties so as to provide an attractive platform to select a variety of properties sought for in Darwinian Chemical Systems (e.g. self-assembly, out-of-equilibrium dynamics, discovery of catalysts).

Project coordination

Ludovic Jullien (Processus d'Activation Sélectif par Transfert d'Energie Uni-électronique ou Radiatif)

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.


I.C.S Institut Charles Sadron (UPR 22)
PASTEUR Processus d'Activation Sélectif par Transfert d'Energie Uni-électronique ou Radiatif
SQPOV Sécurité et Qualité des Produits d'Origine Végétale

Help of the ANR 438,958 euros
Beginning and duration of the scientific project: September 2019 - 42 Months

Useful links

Explorez notre base de projets financés



ANR makes available its datasets on funded projects, click here to find more.

Sign up for the latest news:
Subscribe to our newsletter