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Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro- N -acetylneuraminic acid

Identifieur interne : 002C10 ( Main/Exploration ); précédent : 002C09; suivant : 002C11

Inhibition of neuraminidase activity by derivatives of 2-deoxy-2,3-dehydro- N -acetylneuraminic acid

Auteurs : P. Meindl [Autriche] ; G. Bodo [Autriche] ; P. Palese [États-Unis] ; J. Schulman [États-Unis] ; H. Tuppy [Autriche]

Source :

RBID : ISTEX:8FFBE048372A94739993860AB41F5521DB27C3CD

English descriptors

Abstract

Abstract: Eighteen derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid were assayed for inhibitory activity against neuraminidases from viral and bacterial sources. Twelve of these compounds were active against neuraminidases of Vibrio cholerae, influenza AMel, BLee, and Newcastle disease virus, causing 50% enzyme inhibition in concentrations ranging from 10−3M to 10−6M. The most active of them and the most potent neuraminidase inhibitor described so far is 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid. This compound has an inhibitor constant (Ki) of 7,9 × 10−7, M for influenza AMel virus neuraminidase whereas the Km of the virus enzyme for the substrate is 1000 times weaker (Km = 6, 9 × 10−4M). The mechanism of inhibition is competitive, and enzyme inhibition is independent of enzyme concentration. 2-Deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid inhibits hemagglutination by NDV and SV5 but does not inhibit agglutination of red cells by Sendai virus or influenza A and B viruses.

Url:
DOI: 10.1016/0042-6822(74)90080-4


Affiliations:


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Le document en format XML

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<term>Cholerae neuraminidase</term>
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<div type="abstract" xml:lang="en">Abstract: Eighteen derivatives of 2-deoxy-2,3-dehydro-N-acetylneuraminic acid were assayed for inhibitory activity against neuraminidases from viral and bacterial sources. Twelve of these compounds were active against neuraminidases of Vibrio cholerae, influenza AMel, BLee, and Newcastle disease virus, causing 50% enzyme inhibition in concentrations ranging from 10−3M to 10−6M. The most active of them and the most potent neuraminidase inhibitor described so far is 2-deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid. This compound has an inhibitor constant (Ki) of 7,9 × 10−7, M for influenza AMel virus neuraminidase whereas the Km of the virus enzyme for the substrate is 1000 times weaker (Km = 6, 9 × 10−4M). The mechanism of inhibition is competitive, and enzyme inhibition is independent of enzyme concentration. 2-Deoxy-2,3-dehydro-N-trifluoroacetylneuraminic acid inhibits hemagglutination by NDV and SV5 but does not inhibit agglutination of red cells by Sendai virus or influenza A and B viruses.</div>
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