Assessment of RNA carrier function in peptide amphiphiles derived from the HIV fusion peptide |
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| Institution: | 1. Department of Animal Science, Aarhus University, Blichers Allé 20, P.O. Box 50, DK-8830 Tjele, Denmark;2. Department of Veterinary Disease Biology, University of Copenhagen, DK-1870 Frederiksberg C, Denmark;3. Department of Molecular Biology and Genetics, Aarhus University, Blichers Allé 20, P.O. Box 50, DK-8830 Tjele, Denmark;1. Department of Cancer Research and Molecular Medicine, NTNU, Trondheim, Norway;2. Department of Gastroenterology and Hepatology, St. Olav’s University Hospital, Trondheim, Norway;3. Department of Pathology, St. Olav’s University Hospital, Trondheim, Norway;4. Department of Cell and Molecular Physiology, Institute of Translational Medicine, University of Liverpool, Liverpool, United Kingdom;5. The Central Norway Regional Health Authority, Trondheim, Norway;1. Bor State Hospital, Neurology Clinic, Istasyon Street, 51700 Bor, Nigde, Turkey;2. BezmiAlem Vakif University, Vocational School of Health Services, Medical Laboratory Techniques, Adnan Menderes Bulvar?, 34093 Fatih, Istanbul, Turkey;3. Fatih University, Faculty of Engineering, Department of Genetics and Bioengineering, Buyukcekmece Campus, 34500 Buyukcekmece, Istanbul, Turkey;1. Department of Clinical Sciences, Medicine, Lund University, Sölvegatan 19, 22184 Lund, Sweden;2. Graduate School of Medicine, Akita University, Akita, Japan;3. Yutaka Seino Distinguished Center for Diabetes Research, Kensai Electric Power Medical Research Institute, Kobe, Japan;1. EA7300, Stress Immunity Pathogens Laboratory, Faculty of Medicine, Université de Lorraine, 9 Avenue de la Forêt de Haye, F-54500, Vand?uvre-lès-Nancy, France;2. Molecular and Structural Enzymology Group, Université de Lorraine, IMoPA, UMR 7365, F-54500, Vandoeuvre-lès-Nancy, France |
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| Abstract: | A small library of amphiphilic peptides has been evaluated for duplex RNA carrier function into A549 cells. We studied peptides in which a C-terminal 7-residue cationic domain is attached to a neutral/hydrophobic 23-residue domain that is based on the viral fusion peptide of HIV. We also examined peptides in which the cationic charge was evenly distributed throughout the peptide. Strikingly, subtle sequence variations in the hydrophobic domain that do not alter net hydrophobicity result in wide variation in RNA uptake. Additionally, cyclic cystine variants are much less active as RNA carriers than their open-chain cysteine analogs. With regard to electrostatic effects, we find that lysine is less effective than arginine in facilitating uptake, and that even distribution of cationic residues throughout the peptide sequence results in especially effective RNA carrier function. Overall, minor changes in peptide hydrophobicity, flexibility and charge distribution can significantly alter carrier function. We hypothesize this is due to altered properties of the peptide-RNA assembly rather than peptide secondary structure. |
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| Keywords: | Carrier Amphiphilic peptide Electrostatics Transport Nucleic acids |
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