Trends in Glycoscience and Glycotechnology
Online ISSN : 1883-2113
Print ISSN : 0915-7352
ISSN-L : 0915-7352
MINIREVIEW
Towards Improvement of Covalent Neuraminidase Inhibitors with Anomeric Substitution
Christopher J. VavrickaTatsuma MatsumotoHiromasa Kiyota
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2020 Volume 32 Issue 185 Pages E1-E5

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Abstract

Neuraminidase (NA) inhibitors are effective at treating and preventing infections caused by epidemic and pandemic influenza viruses. The first generation of influenza NA inhibitors were inspired by the structure of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid, a putative oxocarbenium ion transition state analogue. As a next-generation approach to influenza NA inhibitor design, irreversible inhibitors targeting influenza NA Tyr406 are now being explored. After proving the concept that influenza NA can be irreversibly inhibited by difluorosialic acids, substitution of the anomeric carboxy group was examined as a second novel strategy. Anomeric sulfo analogues of sialic acid (N-acetylneuraminic acid, NANA) were thereby synthesized and found to inhibit influenza NA with higher potency relative to that of the corresponding anomeric carboxy and phosphono compounds, via enhanced electrostatic interactions with the NA active site triarginyl cluster. The combination of these two novel approaches is now being pursued to produce improved irreversible NA inhibitors.

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© 2020 FCCA (Forum: Carbohydrates Coming of Age)
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