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Sialyl-LacNAc-PNADNA Concatamers by Rolling-Circle Amplification as Multivalent Inhibitors of Influenza A Virus Particles

V. Bandlow, D. Lauster, K. Ludwig, M. Hilsch, V. Reiter-Scherer, J. P. Rabe, C. Böttcher, A. Herrmann and O. Seitz – 2019

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 10(3) -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 10(4) -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.

Titel
Sialyl-LacNAc-PNADNA Concatamers by Rolling-Circle Amplification as Multivalent Inhibitors of Influenza A Virus Particles
Verfasser
V. Bandlow, D. Lauster, K. Ludwig, M. Hilsch, V. Reiter-Scherer, J. P. Rabe, C. Böttcher, A. Herrmann and O. Seitz
Datum
2019
Kennung
DOI: 10.1002/cbic.201800643
Zitierweise
Chembiochem 2019, 2,159-165
Sprache
eng
Art
Text