Novel 3,4-disubstituted-Neu5Ac2en derivatives as probes to investigate flexibility of the influenza virus sialidase 150-loop
Author(s)
Rudrawar, Santosh
Dyason, Jeffrey C
Maggioni, Andrea
Thomson, Robin J
von Itzstein, Mark
Griffith University Author(s)
Year published
2013
Metadata
Show full item recordAbstract
Novel 3,4-disubstituted-Neu5Ac2en derivatives have been synthesised to probe the open 150-loop conformation of influenza virus sialidases. Both equatorially and axially (epi) substituted C4 amino and guanidino 3-(p-tolyl)allyl-Neu5Ac2en derivatives were prepared, via the 4-epi-hydroxy derivative. The equatorially-substituted 4-amino derivative showed low micromolar inhibition of both group-1 (pdm09 H1N1) and group-2 (pdm57 H2N2) sialidases, and provides the first in vitro evidence that a group-2 sialidase may exhibit 150-loop flexibility.Novel 3,4-disubstituted-Neu5Ac2en derivatives have been synthesised to probe the open 150-loop conformation of influenza virus sialidases. Both equatorially and axially (epi) substituted C4 amino and guanidino 3-(p-tolyl)allyl-Neu5Ac2en derivatives were prepared, via the 4-epi-hydroxy derivative. The equatorially-substituted 4-amino derivative showed low micromolar inhibition of both group-1 (pdm09 H1N1) and group-2 (pdm57 H2N2) sialidases, and provides the first in vitro evidence that a group-2 sialidase may exhibit 150-loop flexibility.
View less >
View less >
Journal Title
Bioorganic Medicinal Chemistry
Volume
21
Issue
16
Subject
Medicinal and biomolecular chemistry
Biologically active molecules
Organic chemistry
Pharmacology and pharmaceutical sciences
Biochemistry and cell biology