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Theses

Conception et application de nouveaux outils photochimiques pour l’étude des récepteurs canaux P2X

Abstract : P2X receptors are cationic ligand-gated ion channels, activated by extracellular ATP, involved in many physio-pathological roles. Their function is associated with different allosteric states. During this PhD, we have designed three new strategies, spanning photochemical organic synthesis and patch-clamp electrophysiology to elucidate the molecular mechanisms involved in these conformational states and to collect data in order to study structure-function relationships. - Synthesis and application of molecular tweezers, which allows the photo-control of P2X Rand the study of molecular motions - Synthesis and characterization of a photo-cleavable amino acid with the aim of incorporating it into P2XR and doing structure-function relationships - Incorporation of an unnatural amino acid for photo-crosslinking studies. We have been able to probe the molecular mechanism involved in large organic cations permeation of P2XR, to bring into question the dilated state and to identify a physiological cation that can flow through P2XR. We have also designed a photo-cleavable amino acid which could serve in the study of structure-function relationships.
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https://tel.archives-ouvertes.fr/tel-01716267
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Submitted on : Friday, February 23, 2018 - 3:01:06 PM
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Laurie Peverini. Conception et application de nouveaux outils photochimiques pour l’étude des récepteurs canaux P2X. Chimie thérapeutique. Université de Strasbourg, 2017. Français. ⟨NNT : 2017STRAF061⟩. ⟨tel-01716267⟩

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