title: A phospha-oseltamivir-biotin conjugate as a strong and selective adhesive for the influenza virus.
abstract: We present the synthesis and application of a molecule containing both the powerful influenza neuraminidase (NA) inhibitor phospha-oseltamivir and d-biotin, connected via an undecaethylene glycol spacer. It inhibits influenza virus neuraminidase (from the H3N2 X31 virus) in the same range as oseltamivir, with a slow off-rate, and produces a stable NA-coated surface when loaded onto streptavidin-coated biosensors. Purified X31 virus binds to these loaded biosensors with an apparent dissociation constant in the low picomolar range and binding of antibodies to the immobilized virus could be readily detected. The compound is thus a potential candidate for the selective immobilization of influenza virus in influenza diagnosis, vaccine choice, development or testing.
authors.affiliation: 18, Tarret Burn, Didcot OX11 7FZ, UK; Chemistry Division, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK. Electronic address: hansstreic@gmail.com.
authors.forename: Hansjörg
authors.initials: H
authors.lastname: Streicher
authors.affiliation: Division of Physical Biochemistry, MRC National Institute of Medical Research, Mill Hill, London NW7 1AA, UK.
authors.forename: Stephen R
authors.initials: SR
authors.lastname: Martin
authors.affiliation: Division of Physical Biochemistry, MRC National Institute of Medical Research, Mill Hill, London NW7 1AA, UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Coombs
authors.affiliation: Division of Virology, MRC National Institute of Medical Research, Mill Hill, London NW7 1AA, UK.
authors.forename: John
authors.initials: J
authors.lastname: McCauley
authors.affiliation: Chemistry Division, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK.
authors.forename: David
authors.initials: D
authors.lastname: Neill-Hall
authors.affiliation: Chemistry Division, School of Life Sciences, University of Sussex, Brighton BN1 9QJ, UK.
authors.forename: Mathew
authors.initials: M
authors.lastname: Stanley
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001710:Biotin / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D008968:Molecular Conformation; D009439:Neuraminidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D009975:Orthomyxoviridae / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D053139:Oseltamivir / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D004791:Enzyme Inhibitors; D053139:Oseltamivir; D001710:Biotin; D009439:Neuraminidase
keywords: Biosensors; Influenza virus; Neuraminidase inhibitor; Oseltamivir; Virus immobilisation