期刊
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
卷 56, 期 21, 页码 5931-5936出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.201702005
关键词
antiviral agents; in vivo studies; influenza virus; multivalency; peptides
资金
- German Science Foundation (DFG) [SFB765, SPP 1623]
- Focus Area Nanoscale of the Freie Universitat Berlin
- Fonds der Chemischen Industrie
- Einstein-Foundation Berlin
- Boehringer-Ingelheim Stiftung (Plus 3 award)
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.
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