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Biophysical investigations of the LAH4 family peptides : enhancer of gene delivery, from peptide-peptide interactions to peptide-membrane interactions

Abstract : The LAH4 family consists of cationic amphiphilic peptides with propensity to fold in α-helical secondary structures. They contain histidines allowing the modulation of their interactions in a pH dependent manner in the physiological range. In membranes, at neutral or acidic pH the peptide assumes a transmembrane or an in planar configuration, respectively.In the field of gene delivery systems, peptides like LAH4 are used. They are able to firstly interact with different cargoes in order to form stable complexes, then interact with the cell membrane, and finally, promote to escape from the endosome.This PhD has been divided into three parts in order to characterize, with biophysical methods, the interactions occurring during the delivery of these gene systems: peptide-peptide interactions with a focus on the study of VF1 fibre formation; peptide-membrane interactions: with the investigation of the effect of LAH4L1 in different membranes; and peptide-DNA interactions, where the interactions of LAH4L1 with a small DNA fragment were measured.
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Justine Wolf. Biophysical investigations of the LAH4 family peptides : enhancer of gene delivery, from peptide-peptide interactions to peptide-membrane interactions. Biological Physics [physics.bio-ph]. Université de Strasbourg, 2018. English. ⟨NNT : 2018STRAF037⟩. ⟨tel-01997993⟩

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