Les acides α-aminés non naturels forment une famille de composés incontournables pour la conception de peptidomimétiques. Plus précisément, l'utilisation du silicium comme isostère du carbone sur la chaîne latérale des acides α-aminés a été largement reportée dans la littérature, montrant alors l'importance d'une telle modification. En particulier, compte tenu du rôle fondamental que joue la proline dans la structuration des peptides, et des avantages que peut apporter le silicium, il nous a paru intéressant de nous centrer sur la silaproline. Après avoir mis au point une synthèse permettant la production de la silaproline à grande échelle, nous avons mis au point la préparation d'homopolypeptides de ce résidu particulier. Dans un premier temps des oligomères monodisperses de silaproline ont été synthétisés. L'étude structurale par RMN, CD et modélisation moléculaire a permis de confirmer la conformation préférentielle en hélice polyproline de type II (PPII). Ensuite la synthèse de polymères plus longs, obtenus par polymérisation de N-carboxyanhydrides a été développée. Ces nouveaux biopolymères ainsi préparés ont conduit à des mimes de PPII lipophiles. Enfin, une nouvelle voie de polymérisation, dans des conditions douces, par réaction d'esters, a été optimisée, permettant d'accéder facilement à des polypeptides. / Unnatural α-amino acids form a family of essential compounds for the design of peptidomimetics. More specifically, the use of silicon as an isostere of carbon on the side chain of α-amino acids has been widely reported in the literature, while demonstrating the importance of this modification. In particular, the fundamental role of proline in peptide structures, and the advantage of the silicon, promoted us to focus on the silaproline.After the development of a gram scale synthesis of silaproline, we prepared homopolypeptides of this particular residue. Firstly, monodisperse silaproline oligomers were synthesized. The structural study by NMR, CD and molecular modeling confirmed the conformational preference for polyproline type II helix (PPII). Then longer polymers were obtained by polymerization of N-carboxyanhydrides. These new biopolymers were prepared, leading to more lipophilic PPII mimics.Finally, a new way of polymerization by reacting esters under mild conditions has been optimized for easy access to polypeptides.

Lightly cross-linked polyelectrolyte microgels are materials with interesting properties for a range of applications. For instance, the volume of these particles can be drastically changed in response to pH, ionic strength, temperature, or the concentration of specific ions and metabolites. In addition, microgel particles can bind substantial amounts of oppositely charged substances, such as proteins and peptides, and release them upon changes in the external environment. Consequently, microgels have potential in catalysis, photonics, biomaterials, and not at least, as protective and stimuli-sensitive carriers for protein and peptide drugs. In this thesis, the interaction between anionic microgels and cationic peptides was investigated by monitoring microgel deswelling and reswelling in response to peptide binding and release using micromanipulator-assisted light microscopy. In addition, peptide distribution in microgels was analyzed with confocal laser scanning microscopy and peptide uptake determined with solution depletion measurements. The aim of the thesis was to clarify how parameters such as peptide size, charge density, pH, ionic strength and hydrophobicity influences the peptide binding to, distribution in and release from, polyelectrolyte microgels. Results obtained in this thesis show that electrostatic attraction is a prerequisite for interaction to occur although non-electrostatic contributions are responsible the finer details of the interactions. The size and charge density of the interacting peptides play a major role, as large and highly charged peptides are restricted to enter and interact with the microgel core, thus displaying a surface-confined distribution. The peptide-microgel interaction strength is highly reflected in the probability of peptides to be detached from the gel network. For instance, reducing the electrostatic interactions by adding salt induces significant peptide release of sufficiently small and moderately charged peptides, whereas longer and more highly charged peptides is retained in the microgel network due to the strong interaction, insufficient salt screening, and gel network pore size restriction. Decreasing the charge density of microgel network and/or peptides increases the probability for peptide detachment tremendously. To summarize, interactions occurring in oppositely charged microgel-peptide systems can be tuned by varying parameters such as charge density and peptide size and through this, the peptide uptake, distribution and release can be controlled to alter the performance of microgels in peptide drug delivery.