Sialyl-LacNAc-PNAâ
DNA Concatamers by Rolling-Circle Amplification as Multivalent Inhibitors of Influenzaâ
A Virus Particles.
Chembiochem
; 20(2): 159-165, 2019 01 18.
Article
em En
| MEDLINE
| ID: mdl-30536690
ABSTRACT
The surfaces of influenzaâ
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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Antivirais
/
Vírion
/
DNA Circular
/
Glicoproteínas de Hemaglutininação de Vírus da Influenza
/
Ácidos Nucleicos Peptídicos
/
Técnicas de Amplificação de Ácido Nucleico
Idioma:
En
Revista:
Chembiochem
Assunto da revista:
BIOQUIMICA
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Alemanha