title: Anti-Hemagglutinin Antibody Derived Lead Peptides for Inhibitors of Influenza Virus Binding.
abstract: 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/Mute Swan/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.
authors.affiliation: Department of Bioanalytics and Biosensorics, Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics and Bioprocesses, Potsdam, Germany.|Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany.
authors.forename: Henry
authors.initials: H
authors.lastname: Memczak
authors.affiliation: Department of Biology, Humboldt Universität zu Berlin, Berlin, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Lauster
authors.affiliation: Department of Theory and Bio-Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Parimal
authors.initials: P
authors.lastname: Kar
authors.affiliation: Department of Biology, Humboldt Universität zu Berlin, Berlin, Germany.|Departamento de Química Biológica e IQUIBICEN-CONICET, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Buenos Aires, Argentina.
authors.forename: Santiago
authors.initials: S
authors.lastname: Di Lella
authors.affiliation: Institute of Immunology, Charité, Berlin, Germany.
authors.forename: Rudolf
authors.initials: R
authors.lastname: Volkmer
authors.affiliation: Department of Theory and Bio-Systems, Max-Planck-Institute of Colloids and Interfaces, Potsdam, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Knecht
authors.affiliation: Department of Biology, Humboldt Universität zu Berlin, Berlin, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Herrmann
authors.affiliation: Department of Bioanalytics and Biosensorics, Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics and Bioprocesses, Potsdam, Germany.
authors.forename: Eva
authors.initials: E
authors.lastname: Ehrentreich-Förster
authors.affiliation: Institute of Biochemistry and Biology, University of Potsdam, Potsdam, Germany.|Department of Biosystem Integration and Automation, Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics and Bioprocesses, Potsdam, Germany.
authors.forename: Frank F
authors.initials: FF
authors.lastname: Bier
authors.affiliation: Department of Bioanalytics and Biosensorics, Fraunhofer Institute for Cell Therapy and Immunology, Branch Bioanalytics and Bioprocesses, Potsdam, Germany.
authors.forename: Walter F M
authors.initials: WF
authors.lastname: Stöcklein
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000276:immunology*; D000914:Antibodies, Viral / Q000276:immunology*; D002460:Cell Line; D004285:Dogs; D000939:Epitopes / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000276:immunology*; D006801:Humans; D007251:Influenza, Human / Q000821:virology*; D056004:Molecular Dynamics Simulation; D053585:Virus Attachment
chemical_list: D057134:Antibodies, Neutralizing; D000914:Antibodies, Viral; D000939:Epitopes; D019267:Hemagglutinin Glycoproteins, Influenza Virus