دورية أكاديمية
Copper-binding anticancer peptides from the piscidin family: an expanded mechanism that encompasses physical and chemical bilayer disruption.
العنوان: | Copper-binding anticancer peptides from the piscidin family: an expanded mechanism that encompasses physical and chemical bilayer disruption. |
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المؤلفون: | Comert F; Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA., Heinrich F; Department of Physics, Carnegie Mellon University, Pittsburgh, PA, 15213, USA.; Center for Neutron Research, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA., Chowdhury A; Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA., Schoeneck M; University of Rochester School of Medicine and Dentistry, Rochester, NY, 14620, USA., Darling C; Department of Biological Sciences, Clemson University, Clemson, SC, 29634, USA., Anderson KW; Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA.; Biomolecular Measurement Division, National Institute of Standards and Technology, Gaithersburg, MD, 20899, USA., Libardo MDJ; Department of Chemistry and Institute of Materials Science, University of Connecticut, Storrs, CT, 06269, USA., Angeles-Boza AM; Department of Chemistry and Institute of Materials Science, University of Connecticut, Storrs, CT, 06269, USA., Silin V; Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA., Cotten ML; Department of Applied Science, William and Mary, Williamsburg, VA, 23185, USA. mcotten@wm.edu., Mihailescu M; Institute for Bioscience and Biotechnology Research, Rockville, MD, 20850, USA. emihailescu@ibbr.umd.edu. |
المصدر: | Scientific reports [Sci Rep] 2021 Jun 16; Vol. 11 (1), pp. 12620. Date of Electronic Publication: 2021 Jun 16. |
نوع المنشور: | Journal Article; Research Support, U.S. Gov't, Non-P.H.S. |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: London : Nature Publishing Group, copyright 2011- |
مواضيع طبية MeSH: | Antineoplastic Agents/*pharmacology , Cell-Penetrating Peptides/*pharmacology , Copper/*chemistry , Lipid Bilayers/*chemistry, A549 Cells ; Antineoplastic Agents/chemistry ; Cell Line, Tumor ; Cell Survival/drug effects ; Cell-Penetrating Peptides/chemistry ; Fish Proteins/chemistry ; Fish Proteins/pharmacology ; HeLa Cells ; Humans ; Lipid Peroxidation ; Models, Molecular |
مستخلص: | In the search for novel broad-spectrum therapeutics to fight chronic infections, inflammation, and cancer, host defense peptides (HDPs) have garnered increasing interest. Characterizing their biologically-active conformations and minimum motifs for function represents a requisite step to developing them into efficacious and safe therapeutics. Here, we demonstrate that metallating HDPs with Cu 2+ is an effective chemical strategy to improve their cytotoxicity on cancer cells. Mechanistically, we find that prepared as Cu 2+ -complexes, the peptides not only physically but also chemically damage lipid membranes. Our testing ground features piscidins 1 and 3 (P1/3), two amphipathic, histidine-rich, membrane-interacting, and cell-penetrating HDPs that are α-helical bound to membranes. To investigate their membrane location, permeabilization effects, and lipid-oxidation capability, we employ neutron reflectometry, impedance spectroscopy, neutron diffraction, and UV spectroscopy. While P1-apo is more potent than P3-apo, metallation boosts their cytotoxicities by up to two- and seven-fold, respectively. Remarkably, P3-Cu 2+ is particularly effective at inserting in bilayers, causing water crevices in the hydrocarbon region and placing Cu 2+ near the double bonds of the acyl chains, as needed to oxidize them. This study points at a new paradigm where complexing HDPs with Cu 2+ to expand their mechanistic reach could be explored to design more potent peptide-based anticancer therapeutics. |
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المشرفين على المادة: | 0 (Antineoplastic Agents) 0 (Cell-Penetrating Peptides) 0 (Fish Proteins) 0 (Lipid Bilayers) 789U1901C5 (Copper) |
تواريخ الأحداث: | Date Created: 20210617 Date Completed: 20211101 Latest Revision: 20240811 |
رمز التحديث: | 20240812 |
مُعرف محوري في PubMed: | PMC8208971 |
DOI: | 10.1038/s41598-021-91670-w |
PMID: | 34135370 |
قاعدة البيانات: | MEDLINE |
تدمد: | 2045-2322 |
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DOI: | 10.1038/s41598-021-91670-w |