Designer Amyloid Cell-Penetrating Peptides for Potential Use as Gene Transfer Vehicles.

Autor: Kokotidou C; Department of Materials Science and Technology, University of Crete, 70013 Heraklion, Grete, Greece.; Institute of Electronic Structure and Laser (IESL) FORTH, 70013 Heraklion, Crete, Greece., Jonnalagadda SVR; Artie McFerrin Department of Chemical Engineering, Texas A&M University College Station, TX 77843-3251, USA., Orr AA; Artie McFerrin Department of Chemical Engineering, Texas A&M University College Station, TX 77843-3251, USA., Vrentzos G; Institute of Molecular Biology and Biotechnology (IMBB) FORTH, 70013 Heraklion, Crete, Greece., Kretsovali A; Institute of Molecular Biology and Biotechnology (IMBB) FORTH, 70013 Heraklion, Crete, Greece., Tamamis P; Artie McFerrin Department of Chemical Engineering, Texas A&M University College Station, TX 77843-3251, USA., Mitraki AA; Department of Materials Science and Technology, University of Crete, 70013 Heraklion, Grete, Greece.; Institute of Electronic Structure and Laser (IESL) FORTH, 70013 Heraklion, Crete, Greece.
Jazyk: angličtina
Zdroj: Biomolecules [Biomolecules] 2019 Dec 18; Vol. 10 (1). Date of Electronic Publication: 2019 Dec 18.
DOI: 10.3390/biom10010007
Abstrakt: Cell-penetrating peptides are used extensively to deliver molecules into cells due to their unique characteristics such as rapid internalization, charge, and non-cytotoxicity. Amyloid fibril biomaterials were reported as gene transfer or retroviral infection enhancers; no cell internalization of the peptides themselves is reported so far. In this study, we focus on two rationally and computationally designed peptides comprised of β-sheet cores derived from naturally occurring protein sequences and designed positively charged and aromatic residues exposed at key residue positions. The β-sheet cores bestow the designed peptides with the ability to self-assemble into amyloid fibrils. The introduction of positively charged and aromatic residues additionally promotes DNA condensation and cell internalization by the self-assembled material formed by the designed peptides. Our results demonstrate that these designer peptide fibrils can efficiently enter mammalian cells while carrying packaged luciferase-encoding plasmid DNA, and they can act as a protein expression enhancer. Interestingly, the peptides additionally exhibited strong antimicrobial activity against the enterobacterium Escherichia coli.
Competing Interests: The authors declare no conflicts of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
Databáze: MEDLINE
Externí odkaz: