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Effect of a Fusion Peptide by Covalent Conjugation of a Mitochondrial Cell-Penetrating Peptide and a Glutathione Analog Peptide
Stockholm University, Faculty of Science, Department of Neurochemistry.
Stockholm University, Faculty of Science, Department of Neurochemistry. University of Tartu, Estonia.
Number of Authors: 2
2017 (English)In: Molecular therapy. Methods & clinical development, ISSN 2399-6951, E-ISSN 2329-0501, Vol. 5, 221-231 p.Article in journal (Refereed) Published
Abstract [en]

Previously, we designed and synthesized a library of mitochondrial antioxidative cell-penetrating peptides (mtCPPs) superior to the parent peptide, SS31, to protect mitochondria from oxidative damage. A library of antioxidative glutathione analogs called glutathione peptides (UPFs), exceptional in hydroxyl radical elimination compared with glutathione, were also designed and synthesized. Here, a follow-up study is described, investigating the effects of the most promising members from both libraries on reactive oxidative species scavenging ability. None of the peptides influenced cell viability at the concentrations used. Fluorescence microscopy studies showed that the fluorescein-mtCPP1-UPF25 (mtgCPP) internalized into cells, and spectrofluorometric analysis determined the presence and extent of peptide into different cell compartments. mtgCPP has superior antioxidative activity compared with mtCPP1 and UPF25 against H2O2 insult, preventing ROS formation by 2- and 3-fold, respectively. Moreover, we neither observed effects on mitochondrial membrane potential nor production of ATP. These data indicate that mtgCPP is targeting mitochondria, protecting them from oxidative damage, while also being present in the cytosol. Our hypothesis is based on a synergistic effect resulting from the fused peptide. The mitochondrial peptide segment is targeting mitochondria, whereas the glutathione analog peptide segment is active in the cytosol, resulting in increased scavenging ability.

Place, publisher, year, edition, pages
2017. Vol. 5, 221-231 p.
Keyword [en]
antioxidants, cell-penetrating peptides, glutathione analogs, superoxide anion scavenging, mitochondrial targeting, mitochondrial membrane potential
National Category
Other Basic Medicine Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy) Biological Sciences
Identifiers
URN: urn:nbn:se:su:diva-145999DOI: 10.1016/j.omtm.2017.04.010ISI: 000406299600022PubMedID: 28567432OAI: oai:DiVA.org:su-145999DiVA: diva2:1136269
Available from: 2017-08-26 Created: 2017-08-26 Last updated: 2017-08-26Bibliographically approved

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Cerrato, Carmine PasqualeLangel, Ülo
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