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Antimicrobial Peptides and Copper(II) Ions: Novel Therapeutic Opportunities
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    Antimicrobial Peptides and Copper(II) Ions: Novel Therapeutic Opportunities
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    • Jasmin Portelinha
      Jasmin Portelinha
      Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
    • Searle S. Duay
      Searle S. Duay
      Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
      Chemistry Department, Adamson University, 900 San Marcelino Street, Ermita, Manila 1000, Philippines
    • Seung I. Yu
      Seung I. Yu
      Department of Molecular and Cell Biology, University of Connecticut, 91 North Eagleville Road, Storrs, Connecticut 06269, United States
      More by Seung I. Yu
    • Kara Heilemann
      Kara Heilemann
      Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
    • M. Daben J. Libardo
      M. Daben J. Libardo
      Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
    • Samuel A. Juliano
      Samuel A. Juliano
      Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
    • Jonathan L. Klassen*
      Jonathan L. Klassen
      Department of Molecular and Cell Biology, University of Connecticut, 91 North Eagleville Road, Storrs, Connecticut 06269, United States
      *M.J.L.K.: email, [email protected]
    • Alfredo M. Angeles-Boza*
      Alfredo M. Angeles-Boza
      Department of Chemistry, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
      Institute of Material Science, University of Connecticut, 55 North Eagleville Road, Storrs, Connecticut 06269, United States
      *A.M.A.-B.: email, [email protected]
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    Chemical Reviews

    Cite this: Chem. Rev. 2021, 121, 4, 2648–2712
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    https://doi.org/10.1021/acs.chemrev.0c00921
    Published February 1, 2021
    Copyright © 2021 American Chemical Society

    Abstract

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    The emergence of new pathogens and multidrug resistant bacteria is an important public health issue that requires the development of novel classes of antibiotics. Antimicrobial peptides (AMPs) are a promising platform with great potential for the identification of new lead compounds that can combat the aforementioned pathogens due to their broad-spectrum antimicrobial activity and relatively low rate of resistance emergence. AMPs of multicellular organisms made their debut four decades ago thanks to ingenious researchers who asked simple questions about the resistance to bacterial infections of insects. Questions such as “Do fruit flies ever get sick?”, combined with pioneering studies, have led to an understanding of AMPs as universal weapons of the immune system. This review focuses on a subclass of AMPs that feature a metal binding motif known as the amino terminal copper and nickel (ATCUN) motif. One of the metal-based strategies of hosts facing a pathogen, it includes wielding the inherent toxicity of copper and deliberately trafficking this metal ion into sites of infection. The sudden increase in the concentration of copper ions in the presence of ATCUN-containing AMPs (ATCUN-AMPs) likely results in a synergistic interaction. Herein, we examine common structural features in ATCUN-AMPs that exist across species, and we highlight unique features that deserve additional attention. We also present the current state of knowledge about the molecular mechanisms behind their antimicrobial activity and the methods available to study this promising class of AMPs.

    Copyright © 2021 American Chemical Society

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    • Sequence similarity network showing the homology relationships between ATCUN-containing AMPs; the largest cluster, cluster 1, displaying the sequence of hepcidin AMPs from a multitude of organisms; cluster 2 is made up of His-rich piscidin AMPs with a highly conserved N-terminus region; cluster 3 showing the conserved DSHH ATCUN motif in histatin AMPs; β-defensin AMPs (cluster 4); cluster 5 shows the highly conserved N- and C-terminus of a group of AMPs derived from ants; myticin family of AMPs (cluster 6); AMPs from human furin-prodomain (cluster 7); wasp (Nasonia vitripennis) AMPs (cluster 8); cluster 9 is made up of amphibian AMPs; cluster 10 that displays the conserved KVHGSL N-terminus region of 40S ribosomal proteins; LEAP-2 AMPs make up cluster 11; α-defensin AMPs (cluster 12); defensins from the Arthropoda phyla make up cluster 13; myticusin AMPs from the Molluska phylum make up cluster 14; β-defensin AMPs with a highly conserved N-terminus and ATCUN sequence (cluster 15); His-rich AMPs from Lucilia sericata (cluster 16); cluster 17 is a small cluster that consists of two amphibian peptides from Pseudophryne giintheri; cluster 18 is made up of AMPs from Gallus gallus or wild chicken; cluster 19 consists of two Attacin AMPs from Hyalophora cecropia; AMPs from Solenopsis invicta (cluster 20); cluster 21 displays the cystatin AMPs from goats or Capra hircus (PDF)

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    Chemical Reviews

    Cite this: Chem. Rev. 2021, 121, 4, 2648–2712
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    https://doi.org/10.1021/acs.chemrev.0c00921
    Published February 1, 2021
    Copyright © 2021 American Chemical Society

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