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Supramolecular Peptide Nanofibrils with Optimized Sequences and Molecular Structures for Efficient Retroviral Transduction

Published version
Peer-reviewed

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Authors

Sieste, S 
Mack, T 
Lump, E 
Hayn, M 
Schütz, D 

Abstract

jats:titleAbstract</jats:title>jats:pAmyloid‐like peptide nanofibrils (PNFs) are abundant in nature providing rich bioactivities and playing both functional and pathological roles. The structural features responsible for their unique bioactivities are, however, still elusive. Supramolecular nanostructures are notoriously challenging to optimize, as sequence changes affect self‐assembly, fibril morphologies, and biorecognition. Herein, the first sequence optimization of PNFs, derived from the peptide enhancing factor‐C (EF‐C, QCKIKQIINMWQ), for enhanced retroviral gene transduction via a multiparameter and a multiscale approach is reported. Retroviral gene transfer is the method of choice for the stable delivery of genetic information into cells offering great perspectives for the treatment of genetic disorders. Single fibril imaging, zeta potential, vibrational spectroscopy, and quantitative retroviral transduction assays provide the structure parameters responsible for PNF assembly, fibrils morphology, secondary and quaternary structure, and PNF‐virus‐cell interactions. Optimized peptide sequences such as the 7‐mer, CKFKFQF, have been obtained quantitatively forming supramolecular nanofibrils with high intermolecular β‐sheet content that efficiently bind virions and attach to cellular membranes revealing efficient retroviral gene transfer.</jats:p>

Description

Funder: German Research Foundation; Id: http://dx.doi.org/10.13039/501100001659

Keywords

peptide nanofibrils, retroviral gene transfer, self&#8208, assembly, structure&#8211, activity relationship

Journal Title

Advanced Functional Materials

Conference Name

Journal ISSN

1616-301X
1616-3028

Volume Title

31

Publisher

Wiley
Sponsorship
Volkswagen Foundation (89943)
Leibniz Association (SAW project)
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