Supramolecular Peptide Nanofibrils with Optimized Sequences and Molecular Structures for Efficient Retroviral Transduction. (22nd February 2021)

• Record Type: Journal Article
• Authors: Sieste, Stefanie; Mack, Thomas; Lump, Edina; Hayn, Manuel; Schütz, Desiree; Röcker, Annika; Meier, Christoph; Kaygisiz, Kübra; Kirchhoff, Frank; Knowles, Tuomas P. J.; Ruggeri, Francesco S.; Synatschke, Christopher V.; Münch, Jan; Weil, Tanja
• Is Part Of: Advanced functional materials. Volume 31:Number 17(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-02-22
• Subjects: peptide nanofibrils -- retroviral gene transfer -- self‐assembly -- structure–activity relationship; Materials -- Periodicals; Chemical vapor deposition -- Periodicals; 620.11
• DOI: 10.1002/adfm.202009382
• Languages: English
• ISSNs: 1616-301X

Abstract

Abstract: Amyloid‐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. Abstract : Enhancing factor‐C (EF‐C), a fragment of the human immunodeficiency virus‐1 glycoprotein, is previously shown to self‐assemble into nanofibrils and enhance viral transduction. Herein, a peptide library based on EF‐C is synthesized through multiparameter and multiscale optimization. It is evaluated for fibril formation, secondary/quaternary structure, virion‐fibril‐cell interaction, and critical parameters for enhanced transduction can be determined in a structure–activity fashion.