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PhD offer - Synthesis of bio-inspired lanthano-peptide catalysts (M/F)

This offer is available in the following languages:
- Français-- Anglais

Application Deadline : 01 May 2025 00:00:00 Paris time

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General information

Offer title : PhD offer - Synthesis of bio-inspired lanthano-peptide catalysts (M/F) (H/F)
Reference : UPR8241-EMIMAT-004
Number of position : 1
Workplace : TOULOUSE
Date of publication : 24 February 2025
Type of Contract : FTC PhD student / Offer for thesis
Contract Period : 36 months
Start date of the thesis : 1 October 2025
Proportion of work : Full Time
Remuneration : 2200 gross monthly
Section(s) CN : 16 - Chemistry of and for life: design and properties of molecules of biological interest

Description of the thesis topic

Lanthanides (Ln) recently joined the family of elements essential to living organisms.[1] The first Ln-enzyme, a methanol dehydrogenase, has been identified. In addition to the redox cofactor pyrroloquinoline quinone (PQQ) responsible for the oxidation of methanol, Ln-MDH contains in its active site a Ln3+ ion bound to PQQ (Figure). Intriguingly, the catalytic activity of this enzyme strongly depends on Ln3+. It is the most active with early Ln3+ (La-Nd), and has no detectable activity with late Ln3+. Due to the difficulty to study the enzyme itself, two alternative approaches have been investigated: (i) the synthesis of molecular complexes mimicking the Ln-PQQ complex;[2] (ii) the use of bio-engineered proteins.[3] In both cases, the catalytic activities were poor to moderate.

The strategy proposed in this project is to combine the advantages of both approaches, thanks to the synthesis of libraries of Ln-binding peptides. Indeed, the choice for a peptide scaffold enables a fast and modular synthesis (as for molecular complexes) and is easily tunable by selecting the appropriate amino acids (as for proteins). The main goal of the project is to obtain structural mimics of the enzyme. The work will be divided in three parts:
(i) Synthesis of non-natural amino acids by organic synthesis, either for Ln-binding or PQQ-coupling;
(ii) Synthesis of peptides library by solid phase peptide synthesis with scaffolds of increasing complexity;
(iii) Physico-chemical analyses (UVvis, luminescence, circular dichroism, NMR) to characterize Ln3+-coordination sphere and peptides stability and structure.

References
[1] a. Daumann, L. J. Essential and Ubiquitous: The Emergence of Lanthanide Metallobiochemistry. Angew. Chem. Int. Ed. 2019, 58 (37), 12795–12802; b. Featherston, E. R.; Cotruvo, J. A. The Biochemistry of Lanthanide Acquisition, Trafficking, and Utilization. Biochim. Biophys. Acta BBA - Mol. Cell Res. 2021, 1868 (1), 118864.
[2] a. McSkimming, A.; Cheisson, T.; Carroll, P. J.; Schelter, E. J. Functional Synthetic Model for the Lanthanide-Dependent Quinoid Alcohol Dehydrogenase Active Site. J. Am. Chem. Soc. 2018, 140 (4), 1223–1226; b. Vetsova, V. A.; Fisher, K. R.; Lumpe, H.; Schäfer, A.; Schneider, E. K.; Weis, P.; Daumann, L. J. Pyrroloquinoline Quinone Aza-Crown Ether Complexes as Biomimetics for Lanthanide and Calcium Dependent Alcohol Dehydrogenases. Chem. – Eur. J. 2021, 27 (39), 10087–10098.
[3] Thompson, P. J.; Boggs, D. G.; Wilson, C. A.; Bruchs, A. T.; Velidandla, U.; Bridwell-Rabb, J.; Olshansky, L. Structure-Driven Development of a Biomimetic Rare Earth Artificial Metalloprotein. Proc. Natl. Acad. Sci. 2024, 121 (33), e2405836121.

Work Context

Environment: The successful candidate will work in an exciting, dynamic and international environment at the Coordination Chemistry Laboratory of the CNRS in Toulouse, France, in the team ALAMBIC. The technical and scientific environment is of high quality and fully adequate for the realisation of the project.

Profile: We are looking for a highly motivated student with a background in molecular chemistry, strong synthetic skills and excellent grades. Applicants should have a strong interest in multidisciplinary projects in the field of bio-inorganic chemistry. In addition, ability to write a scientific report, and strong teamwork skills are required.

Constraints and risks

n/a