In:
Angewandte Chemie, Wiley, Vol. 128, No. 48 ( 2016-11-21), p. 15202-15206
Abstract:
Glycoside hydrolases (GHs) have attracted considerable attention as targets for therapeutic agents, and thus mechanism‐based inhibitors are of great interest. We report the first structural analysis of a carbocyclic mechanism‐based GH inactivator, the results of which show that the two Michaelis complexes are in 2 H 3 conformations. We also report the synthesis and reactivity of a fluorinated analogue and the structure of its covalently linked intermediate (flattened 2 H 3 half‐chair). We conclude that these inactivator reactions mainly involve motion of the pseudo‐anomeric carbon atom, knowledge that should stimulate the design of new transition‐state analogues for use as chemical biology tools.
Type of Medium:
Online Resource
ISSN:
0044-8249
,
1521-3757
DOI:
10.1002/ange.v128.48
DOI:
10.1002/ange.201607431
Language:
English
Publisher:
Wiley
Publication Date:
2016
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505868-5
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506609-8
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514305-6
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505872-7
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1479266-7
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505867-3
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506259-7
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