Sialyl-LacNAc-PNA⋅DNA Concatamers by Rolling-Circle Amplification as Multivalent Inhibitors of Influenza A Virus Particles
| Autor: | Valentin Reiter-Scherer, Jürgen P. Rabe, Malte Hilsch, Christoph Böttcher, Daniel Lauster, Andreas Herrmann, Kai Ludwig, Oliver Seitz, Victor Bandlow |
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| Rok vydání: | 2018 |
| Předmět: |
Peptide Nucleic Acids
Hemagglutinin Glycoproteins Influenza Virus 010402 general chemistry medicine.disease_cause 01 natural sciences Biochemistry Antiviral Agents Virus Bivalent (genetics) 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Influenza A virus medicine A-DNA Trisaccharide Molecular Biology chemistry.chemical_classification Chemistry Organic Chemistry Virion 0104 chemical sciences Rolling circle replication Biophysics Molecular Medicine DNA Circular Nucleic Acid Amplification Techniques DNA 030215 immunology Conjugate |
| Zdroj: | Chembiochem : a European journal of chemical biology. 20(2) |
| ISSN: | 1439-7633 |
| Popis: | The surfaces of influenza A virus (IAV) particles are packed with hundreds of homo-trimeric hemagglutinins (HAs). Monovalent sugars have low affinity for HA, but distance-optimized bivalent sialyl-LacNAc (SLN) conjugates bind it with 103 -fold enhanced potency. Herein, we describe the oligomerization of distance-optimized bivalent binders by branched and linear hybridization on long repetitive DNA templates. The most effective complexes fully inhibited IAVs at a DNA template concentration of 10-9 m. Although a 10-2 m concentration of free trisaccharide ligand is required for full inhibition of the virus, DNA templating enables a 104 -fold reduction in the amount of sugar required. Notably, hybridization-induced rigidification of the DNA templates increased the serospecificity. Cryo-TEM analysis revealed that both spaghetti-type linear forms and cotton-ball-like clusters are able to bridge several adjacent HA molecules on the IAV surface. Programmed self-assembly of ligand-nucleic acid conjugates on long DNA templates might provide generic access to target-specific, high-affinity binders of proteins on globular objects such as cells and viruses. |
| Databáze: | OpenAIRE |
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