# Oral communication: Uranyl-binding peptides to shed light on uranium toxicity at the molecular level

Sarah Hostachy, Fanny Laporte, Yves Chenavier, Alexandra Botz, Christelle

Gateau, Colette Lebrun, Claude Vidaud, Pascale Delangle

► To cite this version:

Sarah Hostachy, Fanny Laporte, Yves Chenavier, Alexandra Botz, Christelle Gateau, et al.. Oral communication: Uranyl-binding peptides to shed light on uranium toxicity at the molecular level. 11th international conference on f-elements, Aug 2023, Strasbourg, France. hal-04827201

HAL Id: hal-04827201

https://hal.science/hal-04827201v1

Submitted on 19 Jun 2025

HAL is a multi-disciplinary open access
archive for the deposit and dissemination of sci-
entific research documents, whether they are pub-
lished or not. The documents may come from
teaching and research institutions in France or
abroad, or from public or private research centers.

L'archive ouverte pluridisciplinaire HAL, est
destinée au dépôt et à la diffusion de documents
scientifiques de niveau recherche, publiés ou non,
émanant des établissements d'enseignement et de
recherche français ou étrangers, des laboratoires
publics ou privés.

<figure><img src="image_1.png" /></figure>

Distributed under a Creative Commons Attribution 4.0 International License
# Uranyl-binding peptides to shed light on uranium toxicity at the molecular level

*Oral communication at the 11th International conference on f-elements, Strasbourg, France, 2023*

Sarah Hostachy,ª Fanny Laporte,ª Yves Chenavier,ª Alexandra Botz,ª Christelle Gateau,ª Colette Lebrun,ª Claude Vidaud,ᵇ Pascale Delangleª*

a. IRIG, SyMMES (UMR5819 Université Grenoble Alpes, CEA, CNRS, Grenoble INP), Grenoble, France

b. CEA, Biosciences and Biotechnologies Institute of Aix-Marseille, Bagnols sur Céze, France

Uranium is a natural element widely found in the environment, which presents radiological and chemical toxicities. This metal most stable form in vivo is the uranyl cation $UO_2^{2+}$, which prefers four to six oxygen donors in its equatorial plane, perpendicular to O-U-O bonds. Understanding the molecular interactions responsible for its toxicity is key to predict the effect of uranium on living organisms and to help in designing efficient detoxification agents.

Our laboratory develops biomimetic approaches, exploiting constrained peptides, to shed light on uranium binding to biomolecules.[1] We designed a series of cyclic decapeptides binding uranyl through the oxygen donors from aspartates or glutamates and phosphoserines. A phosphate-rich peptide demonstrated a very large affinity for uranyl, which is reminiscent of uranium binding by one of the most affine native uranium target, osteopontin.[2] We also designed an original uranyl-binding fluorescent probe, based on a peptidic rigid turn structure that pre-orsents two unnatural amino acid side chains to coordinate uranyl in the equatorial plane. This probe shows an affinity for $UO_2^{2+}$ in the range of those of native proteins, and fluorescent properties that enable the detection of uranyl binding in biological media.[3] It was validated thanks to the well-characterized cyclic decapeptides and allowed us to evaluate the uranyl-binding affinity of four native proteins.

The biomimetic strategies presented here show the power of peptide design to decipher interactions of

<figure><img src="image_2.png" /></figure>

metal ions with biomolecules, interactions which are highly related to their toxicity.

A fluorescent uranyl-binding peptide to evaluate uranyl-protein affinities

## References

[1] A. Garai, P. Delangle, J. Inorg. Biochem. 2020, 203, 110936.

[2] F. A. Laporte, C. Lebrun, C. Vidaud, P. Delangle, Chem. – Eur. J. 2019, 25, 8570–8578.
[3] F. Laporte, Y. Chenavier, A. Botz, C. Gateau, C. Lebrun, S. Hostachy, C. Vidaud, P. Delangle, Angew. Chem. Int. Ed. 2022, 61, e202203198.