Sialyl-LacNac-PNA-DNA concatamers by rolling circle amplification as multivalent inhibitors for Influenza A virus particles

V. Bandlow, D. Lauster, K. Ludwig, M. Hirsch, V. Reiter-Scherer, J.P. Rabe, C. Böttcher, A. Herrmann, 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 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.

Titel
Sialyl-LacNac-PNA-DNA concatamers by rolling circle amplification as multivalent inhibitors for Influenza A virus particles
Verfasser
V. Bandlow, D. Lauster, K. Ludwig, M. Hirsch, V. Reiter-Scherer, J.P. Rabe, C. Böttcher, A. Herrmann, O. Seitz
Datum
2019
Kennung
10.1002/cbic.201800643
Zitierweise
ChemBioChem 2019, 20 (2), 159-165
Art
Text
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