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Préparation de structures amphiphiles de type télomère ou polymère. Applications au domaine biomédical pour la stabilisation de protéines membranaires et le transport de principes actifs

Abstract : In this work we describe the synthesis and the physico-chemical studies of amphiphilic cotelomers derived from Tris(hydroxymethyl)acrylamidomethane (THAM). These molecules could be used either to maintain integral membrane proteins in aqueous solution or as amphiphilic macromolecular drug carrier. After a short review on THAM derivatives, the synthesis of several THAM-based monomers and the characterization of the related kinetic of free radical polymerization are reported in a first chapter. The results showed that the high reactivity of this monomer was essentially due to the strong intermolecular hydrogen bonds established between THAM hydroxyl functions. The second chapter is dedicated to the synthesis of amphiphilic THAM-based cotelomers called amphipols. Such short macromolecules are able to maintain an integral membrane protein (IMP) in aqueous solution under its native form for many weeks. Neutral amphipols were found to strongly bind the transmembrane domain of the IMPs and thus leading to the formation of long-term stable complexes. The third chapter introduces the drug carrying-targetting aspect and explains the most recent works based on this concept. It also describes the synthesis of associative amphiphilic THAM-based polymers that were designed as drug carriers. The rheological studies gave some encouraging preliminary results and revealed the importance of the involved strategy pathway. Indeed, we observed that the method of synthesis affected both the associative properties and the behavior in aqueous solution of the yielded polymers.
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Fabrice Giusti. Préparation de structures amphiphiles de type télomère ou polymère. Applications au domaine biomédical pour la stabilisation de protéines membranaires et le transport de principes actifs. Chimie organique. Université d'Avignon et des Pays du Vaucluse, 2000. Français. ⟨tel-02899603⟩

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