Data: 12/08/2026 - Horário: 10:00 - Local: AUD II, DQ, ICEx
Título: Supramolecular assemblies of histidine-rich designer peptides with multiple biological functions
A ser apresentado por: Burkhard Bechinger - Université de Strasbourg - França
Resumo
A family of designed histidine-rich peptides will be presented which can assemble in a number of different aggregation states. Interestingly, whereas sequences that occur in soluble form exhibit considerable antimicrobial activities, nucleic acid transfection is best by peptides that form large complexes of tuneable size with nucleic acids (DNA, siRNA, mRNA) and these also exhibit strong cell penetrating activities for large proteins, peptide vaccines, adeno associated viruses and nanodots. Due to the presence of four histidines their membrane interactions are strongly pH dependent. The delivery of cargo by these peptides is complex, involving many steps, which we investigated on a structural and biophysical level. More recently, vectofusin-1, a member of the same family of LAH4 peptides has been shown to spontaneously self-assemble into helical oligomers, spherical aggregates, that further assemble into annular and extended nanofibrils and hydrogels as a function of phosphate concentration and in a pH-dependent manner. This bears considerable interest for the design of biomaterials. Importantly, the peptide has a strong capacity to enhance the gene transfer by lentiviral vectors into the cell interior. Thereby, the fibres formed by this relatively short sequence have therapeutic applications ranging from monogenic and infectious diseases to cancer, by enhancing transduction levels of target cells and reducing the amount of lentivirus for greater safety and reduced costs. Vectofusin-1 associates with viral particles and promotes the entry of several retroviral pseudotypes into target cells when added to the culture medium, without cytotoxicity. The vectofusin-1 fibrils have a unique coiled-coil ?-helical structure whereas most other viral transduction enhancers form ?-amyloid fibrils and are investigated by solid-state NMR and other biophysical approaches. Our observations define vectofusin-1 as a member of a new class of ?-helical lentiviral transduction enhancers. Its coiled-coil fibril formation is reversible which bears considerable advantages in handling the peptide in conditions of gene therapy protocols.
