tetano
Editor, Senior Moderator
Chembiochem. 2018 Dec 10. doi: 10.1002/cbic.201800643. [Epub ahead of print]
[h=1]Sialyl-LacNAc-PNA∙DNA concatamers by rolling circle amplification as multivalent inhibitors for Influenza A virus particles.[/h] Bandlow V[SUP]1[/SUP], Lauster D[SUP]1[/SUP], Ludwig K[SUP]1[/SUP], Hilsch M[SUP]1[/SUP], Reiter-Scherer V[SUP]1[/SUP], B?ttcher C[SUP]1[/SUP], Rabe J[SUP]1[/SUP], Herrmann A[SUP]1[/SUP], Seitz O[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The surface of influenza A virus (IAV) particles is packed with hundreds of homo-trimeric hemagglutinins (HA). Monovalent sugars have low affinity but distance optimized bi- or trivalent sialyl-LacNAc (SLN) conjugates bind HA with 10?─10⁴-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 10?⁹ M concentration of DNA template. While a 10?? M concentration of free trisaccharide ligand is required for full inhibition of the virus, DNA-templating enables a 10⁴-fold reduction of the sugar amount. Of note, hybridization-induced rigidification of 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 may provide generic access to target-specific high affinity binders of proteins on globular objects such as cells and viruses.
[h=4]KEYWORDS:[/h] DNA; Influenza Inhibitor; Multivalency; PNA; Rolling Circle Amplification
PMID: 30536690 DOI: 10.1002/cbic.201800643
[h=1]Sialyl-LacNAc-PNA∙DNA concatamers by rolling circle amplification as multivalent inhibitors for Influenza A virus particles.[/h] Bandlow V[SUP]1[/SUP], Lauster D[SUP]1[/SUP], Ludwig K[SUP]1[/SUP], Hilsch M[SUP]1[/SUP], Reiter-Scherer V[SUP]1[/SUP], B?ttcher C[SUP]1[/SUP], Rabe J[SUP]1[/SUP], Herrmann A[SUP]1[/SUP], Seitz O[SUP]2[/SUP].
[h=3]Author information[/h]
[h=3]Abstract[/h] The surface of influenza A virus (IAV) particles is packed with hundreds of homo-trimeric hemagglutinins (HA). Monovalent sugars have low affinity but distance optimized bi- or trivalent sialyl-LacNAc (SLN) conjugates bind HA with 10?─10⁴-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 10?⁹ M concentration of DNA template. While a 10?? M concentration of free trisaccharide ligand is required for full inhibition of the virus, DNA-templating enables a 10⁴-fold reduction of the sugar amount. Of note, hybridization-induced rigidification of 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 may provide generic access to target-specific high affinity binders of proteins on globular objects such as cells and viruses.
[h=4]KEYWORDS:[/h] DNA; Influenza Inhibitor; Multivalency; PNA; Rolling Circle Amplification
PMID: 30536690 DOI: 10.1002/cbic.201800643