Multivalent Peptide–Nanoparticle Conjugates for Influenza‐Virus Inhibition. Issue 21 (26th April 2017)

• Record Type: Journal Article
• Authors: Lauster, Daniel; Glanz, Maria; Bardua, Markus; Ludwig, Kai; Hellmund, Markus; Hoffmann, Ute; Hamann, Alf; Böttcher, Christoph; Haag, Rainer; Hackenberger, Christian P. R.; Herrmann, Andreas
• Is Part Of: Angewandte Chemie international edition. Volume 56:Issue 21(2017)
• Page Start: 5931
• Page End: 5936
• Publication Date: 2017-04-26
• Subjects: antiviral agents -- in vivo studies -- influenza virus -- multivalency -- peptides; Chemistry -- Periodicals; 540
• DOI: 10.1002/anie.201702005
• Languages: English
• ISSNs: 1433-7851

Abstract

Abstract: To inhibit binding of the influenza A virus to the host cell glycocalyx, we generate multivalent peptide–polymer nanoparticles binding with nanomolar affinity to the virus via its spike protein hemagglutinin. The chosen dendritic polyglycerol scaffolds are highly biocompatible and well suited for a multivalent presentation. We could demonstrate in vitro that by increasing the size of the polymer scaffold and adjusting the peptide density, viral infection is drastically reduced. Such a peptide–polymer conjugate qualified also in an in vivo infection scenario. With this study we introduce the first non‐carbohydrate‐based, covalently linked, multivalent virus inhibitor in the nano‐ to picomolar range by ensuring low peptide‐ligand density on a larger dendritic scaffold. Abstract : Peptides against viruses : Multivalent peptide–polymer nanoparticles are used as cellular‐entry blockers for the influenza A virus. Different polymer sizes and ligand densities are compared for an effective cellular infection. It could be shown that the peptide–polymer conjugates are effective in in vitro and also in in vivo studies.