Membrane pore-formation correlates with the hydrophilic angle of histidine-rich amphipathic peptides with multiple biological activities.
Fiche publication
Date publication
février 2020
Journal
Biochimica et biophysica acta. Biomembranes
Auteurs
Membres identifiés du Cancéropôle Est :
Pr BECHINGER Burkhard, Dr KICHLER Antoine
Tous les auteurs :
Lointier M, Aisenbrey C, Marquette A, Tan JH, Kichler A, Bechinger B
Lien Pubmed
Résumé
The LAH4 family of amphipathic peptides exhibits pronounced antimicrobial, cell penetrating and nucleic acid transfection activities. Furthermore, variants were designed with potent lentiviral transduction enhancement. When viewed along a helical wheel the four histidines are arranged to form an amphipathic arrangement. In order to optimize some of these biological activities the number of leucine and alanine residues exposed to the hydrophilic surface was systematically varied which resulted in the design of vectofusin a peptide with strong lentiviral transduction enhancement activities. Here the series of peptides with varying numbers of alanine or leucine residues framed by the histidines was tested for their calcein release activity. Interestingly, the membrane pore formation and DNA transfection activities show a clear correlation with the hydrophilic angle. In contrast the membrane partitioning and the propensity to adopt helical conformations was hardly affected as long as the hydrophilic angle did not exceed a limiting value of 150°.
Mots clés
Amphipathic helix, Antimicrobial peptide, Cell penetrating peptide, Lentiviral transduction, Membrane partitioning, Transfection
Référence
Biochim Biophys Acta Biomembr. 2020 Feb 11;:183212