Angewandte Chemie - International Edition
Angewandte Chemie - International Edition
5 years ago

Multivalent Peptide–Nanoparticle Conjugates for Influenza-Virus Inhibition

Multivalent Peptide–Nanoparticle Conjugates for Influenza-Virus Inhibition
Daniel Lauster, Christian P. R. Hackenberger, Ute Hoffmann, Maria Glanz, Rainer Haag, Andreas Herrmann, Christoph Böttcher, Markus Bardua, Markus Hellmund, Kai Ludwig, Alf Hamann
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. 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.

Publisher URL: http://onlinelibrary.wiley.com/resolve/doi

DOI: 10.1002/anie.201702005

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