TY - JOUR A1 - Memczak, Henry A1 - Lauster, Daniel A1 - Kar, Parimal A1 - Di Lella, Santiago A1 - Volkmer, Rudolf A1 - Knecht, Volker A1 - Herrmann, Andreas A1 - Ehrentreich-Foerster, Eva A1 - Bier, Frank Fabian A1 - Stoecklein, Walter F. M. T1 - Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding JF - PLoS one N2 - 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 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. Y1 - 2016 U6 - https://doi.org/10.1371/journal.pone.0159074 SN - 1932-6203 VL - 11 SP - 82 EP - 90 PB - PLoS CY - San Fransisco ER - TY - GEN A1 - Memczak, Henry A1 - Lauster, Daniel A1 - Kar, Parimal A1 - Di Lella, Santiago A1 - Volkmer, Rudolf A1 - Knecht, Volker A1 - Herrmann, Andreas A1 - Ehrentreich-Förster, Eva A1 - Bier, Frank Fabian A1 - Stöcklein, Walter F. M. T1 - Anti-hemagglutinin antibody derived lead peptides for inhibitors of influenza virus binding T2 - Postprints der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe N2 - 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 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. T3 - Zweitveröffentlichungen der Universität Potsdam : Mathematisch-Naturwissenschaftliche Reihe - 536 KW - receptor-binding KW - A viruses KW - neutralizing antibody KW - avian influenza KW - origin KW - neuraminidase KW - invection KW - entry KW - sites KW - identification Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:kobv:517-opus4-410872 SN - 1866-8372 IS - 536 ER -