Journal
JOURNAL OF PEPTIDE SCIENCE
Volume 23, Issue 4, Pages 320-328Publisher
WILEY
DOI: 10.1002/psc.2955
Keywords
cell-penetrating peptide; amphipathic helix; histidine; phosphatidylserine; phospholipid bilayer; endosomal membrane; DNA transfection; protein transduction
Funding
- Agence Nationale de la Recherche [07-PCV-0018, 14-CE34-0001-01, 10-LABX-0026_CSC]
- University of Strasbourg
- CNRS
- Region Alsace
- RTRA International Center of Frontier Research in Chemistry
- Vaincre la Mucoviscidose
- French Foundation for Medical Research (FRM)
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The histidine-rich designer peptides of the LAH4 family exhibit potent antimicrobial, transfection, transduction and cell-penetrating properties. They form non-covalent complexes with their cargo, which often carry a negative overall charge at pH 7.4 and include a large range of molecules and structures such as oligonucleotides, including siRNA and DNA, peptides, proteins, nanodots and adeno-associated viruses. These complexes are thought to enter the cells through an endosomal pathway where the acidification of the organelle is essential for efficient endosomal escape. Biophysical measurements indicate that, upon acidification, almost half the peptides are released from DNA cargo, leading to the suggestion of a self-promoted uptake mechanism where the liberated peptides lyse the endosomal membranes. LAH4 derivatives also help in cellular transduction using lentiviruses. Here, we compare the DNA transfection activities of LAH4 derivatives, which vary in overall charge and/or the composition in the hydrophobic core region. In addition, LAH4 is shown to mediate the transport of functional -galactosidase, a large tetrameric protein of about 0.5MDa, into the cell interior. Interestingly, the LAH1 peptide efficiently imports this protein, while it is inefficient during DNA transfection assays. Copyright (c) 2017 European Peptide Society and John Wiley & Sons, Ltd.
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