- Antibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/MuteSwan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by aAntibodies against spike proteins of influenza are used as a tool for characterization of viruses and therapeutic approaches. However, development, production and quality control of antibodies is expensive and time consuming. To circumvent these difficulties, three peptides were derived from complementarity determining regions of an antibody heavy chain against influenza A spike glycoprotein. Their binding properties were studied experimentally, and by molecular dynamics simulations. Two peptide candidates showed binding to influenza A/Aichi/2/68 H3N2. One of them, termed PeB, with the highest affinity prevented binding to and infection of target cells in the micromolar region without any cytotoxic effect. PeB matches best the conserved receptor binding site of hemagglutinin. PeB bound also to other medical relevant influenza strains, such as human-pathogenic A/California/7/2009 H1N1, and avian-pathogenic A/MuteSwan/Rostock/R901/2006 H7N1. Strategies to improve the affinity and to adapt specificity are discussed and exemplified by a double amino acid substituted peptide, obtained by substitutional analysis. The peptides and their derivatives are of great potential for drug development as well as biosensing.…
MetadatenVerfasserangaben: | Henry MemczakGND, Daniel Lauster, Parimal KarORCiD, Santiago Di Lella, Rudolf Volkmer, Volker Knecht, Andreas HerrmannORCiD, Eva Ehrentreich-Förster, Frank Fabian BierORCiDGND, Walter F. M. Stöcklein |
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URN: | urn:nbn:de:kobv:517-opus4-410872 |
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DOI: | https://doi.org/10.25932/publishup-41087 |
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ISSN: | 1866-8372 |
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Titel des übergeordneten Werks (Englisch): | Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe |
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Schriftenreihe (Bandnummer): | Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe (536) |
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Publikationstyp: | Postprint |
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Sprache: | Englisch |
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Datum der Erstveröffentlichung: | 18.01.2019 |
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Erscheinungsjahr: | 2016 |
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Veröffentlichende Institution: | Universität Potsdam |
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Datum der Freischaltung: | 18.01.2019 |
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Freies Schlagwort / Tag: | A viruses; avian influenza; entry; identification; invection; neuraminidase; neutralizing antibody; origin; receptor-binding; sites |
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Ausgabe: | 536 |
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Seitenanzahl: | 24 |
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Quelle: | PLOS ONE 11 (2016) 7, Art. e0159074 DOI 10.1371/journal.pone.0159074 |
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Organisationseinheiten: | Mathematisch-Naturwissenschaftliche Fakultät |
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DDC-Klassifikation: | 5 Naturwissenschaften und Mathematik / 50 Naturwissenschaften / 500 Naturwissenschaften und Mathematik |
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| 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
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Peer Review: | Referiert |
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Publikationsweg: | Open Access |
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Fördermittelquelle: | Public Library of Science (PLOS) |
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Lizenz (Deutsch): | CC-BY - Namensnennung 4.0 International |
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