{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T01:59:36Z","timestamp":1762999176671,"version":"build-2065373602"},"reference-count":72,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2016,7,16]],"date-time":"2016-07-16T00:00:00Z","timestamp":1468627200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Toxin\u2013antitoxin systems constitute a native survival strategy of pathogenic bacteria and thus are potential targets of antibiotic drugs. Here, we target the Zeta\u2013Epsilon toxin\u2013antitoxin system, which is responsible for the stable maintenance of certain multiresistance plasmids in Gram-positive bacteria. Peptide ligands were designed on the basis of the \u03b52\u03b62 complex. Three \u03b1 helices of Zeta forming the protein\u2013protein interaction (PPI) site were selected and peptides were designed conserving the residues interacting with Epsilon antitoxin while substituting residues binding intramolecularly to other parts of Zeta. Designed peptides were synthesized with an N-terminal fluoresceinyl-carboxy-residue for binding assays and provided active ligands, which were used to define the hot spots of the \u03b52\u03b62 complex. Further shortening and modification of the binding peptides provided ligands with affinities &lt;100 nM, allowing us to determine the most relevant PPIs and implement a robust competition binding assay.<\/jats:p>","DOI":"10.3390\/toxins8070222","type":"journal-article","created":{"date-parts":[[2016,7,18]],"date-time":"2016-07-18T09:38:03Z","timestamp":1468834683000},"page":"222","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Mapping Protein\u2013Protein Interactions of the Resistance-Related Bacterial Zeta Toxin\u2013Epsilon Antitoxin Complex (\u03b52\u03b62) with High Affinity Peptide Ligands Using Fluorescence Polarization"],"prefix":"10.3390","volume":"8","author":[{"given":"Mar\u00eda","family":"Fern\u00e1ndez-Bachiller","sequence":"first","affiliation":[{"name":"Institute of Pharmacy, Pharmaceutical and Medicinal Chemistry, Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Str. 2+4, 14195 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Iwona","family":"Brzozowska","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics, PAS, Pawi\u0144skiego 5a, 02-106 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Norbert","family":"Odolczyk","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics, PAS, Pawi\u0144skiego 5a, 02-106 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Urszula","family":"Zielenkiewicz","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics, PAS, Pawi\u0144skiego 5a, 02-106 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Piotr","family":"Zielenkiewicz","sequence":"additional","affiliation":[{"name":"Institute of Biochemistry and Biophysics, PAS, Pawi\u0144skiego 5a, 02-106 Warszawa, Poland"},{"name":"Faculty of Biology, Warsaw University, Miecznikowa 1, 02-106 Warszawa, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00f6rg","family":"Rademann","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Pharmaceutical and Medicinal Chemistry, Freie Universit\u00e4t Berlin, K\u00f6nigin-Luise-Str. 2+4, 14195 Berlin, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2016,7,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fpubh.2014.00145","article-title":"The antimicrobial resistance crisis: Causes, consequences, and management","volume":"2","author":"Michael","year":"2014","journal-title":"Front. 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