The synthesis and biological evaluation of lactose-based sialylmimetics as inhibitors of rotaviral infection
Author(s)
Liakatos, A
Kiefel, MJ
Fleming, F
Coulson, B
von Itzstein, M
Year published
2006
Metadata
Show full item recordAbstract
Rotaviruses are the most significant cause of gastroenteritis in young children and are responsible for over 600,000 infant deaths annually. The rotaviral haemagglutinin protein (VP8*) of some strains has been implicated in early recognition and binding events of host cell-surface sialoglycoconjugates, and is therefore an attractive target for potential therapeutic intervention. Since N-acetylneuraminic acid a(2,3)-linked to galactose is believed to be the minimum binding epitope of rotavirus to host cells, we report here our development of an efficient and flexible synthetic route to a range of lactose-based sialylmimetics ...
View more >Rotaviruses are the most significant cause of gastroenteritis in young children and are responsible for over 600,000 infant deaths annually. The rotaviral haemagglutinin protein (VP8*) of some strains has been implicated in early recognition and binding events of host cell-surface sialoglycoconjugates, and is therefore an attractive target for potential therapeutic intervention. Since N-acetylneuraminic acid a(2,3)-linked to galactose is believed to be the minimum binding epitope of rotavirus to host cells, we report here our development of an efficient and flexible synthetic route to a range of lactose-based sialylmimetics of a(2,3)-linked thiosialosides. These compounds were biologically evaluated as inhibitors of rotaviral infection using an in vitro neutralisation assay. The results suggest that these lactose-based sialylmimetics are not inhibitors of the rhesus rotavirus strain; however, they do exhibit modest inhibition of the human (Wa) strain, presumably through inhibition of the rotaviral adhesion process.
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View more >Rotaviruses are the most significant cause of gastroenteritis in young children and are responsible for over 600,000 infant deaths annually. The rotaviral haemagglutinin protein (VP8*) of some strains has been implicated in early recognition and binding events of host cell-surface sialoglycoconjugates, and is therefore an attractive target for potential therapeutic intervention. Since N-acetylneuraminic acid a(2,3)-linked to galactose is believed to be the minimum binding epitope of rotavirus to host cells, we report here our development of an efficient and flexible synthetic route to a range of lactose-based sialylmimetics of a(2,3)-linked thiosialosides. These compounds were biologically evaluated as inhibitors of rotaviral infection using an in vitro neutralisation assay. The results suggest that these lactose-based sialylmimetics are not inhibitors of the rhesus rotavirus strain; however, they do exhibit modest inhibition of the human (Wa) strain, presumably through inhibition of the rotaviral adhesion process.
View less >
Journal Title
Bioorganic & Medicinal Chemistry
Volume
14
Publisher URI
Subject
Medicinal and biomolecular chemistry
Organic chemistry
Pharmacology and pharmaceutical sciences
Biochemistry and cell biology