αβ,α′β′-Diepoxyketones are mechanism-based inhibitors of nucleophilic cysteine enzymes-Reference-Cited by-同舟云学术

αβ,α′β′-Diepoxyketones are mechanism-based inhibitors of nucleophilic cysteine enzymes

Published:2023 Issue:86 Volume:59 Page:12859-12862
ISSN:1359-7345
Container-title:Chemical Communications
language:en
Short-container-title:Chem. Commun.

Author:

de Munnik Mariska¹^ORCID,Lithgow Jasper¹,Brewitz Lennart¹^ORCID,Christensen Kirsten E.²,Bates Robert H.³^ORCID,Rodriguez-Miquel Beatriz³^ORCID,Schofield Christopher J.¹^ORCID

Affiliation:

1. Chemistry Research Laboratory, Department of Chemistry and the Ineos Oxford Institute of Antimicrobial Research, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK

2. Chemical Crystallography, Chemistry Research Laboratory, Department of Chemistry, University of Oxford, 12 Mansfield Road, Oxford, OX1 3TA, UK

3. Tres Cantos Medicines Development Campus, GlaxoSmithKline, Calle Severo Ochoa 2, Tres Cantos, Madrid, Spain

Abstract

αβ,α′β′-Diepoxyketones (DEKs) inhibit nucleophilic cysteine enzymes. DEKs react with a transpeptidase and the SARS-CoV-2 main protease via epoxide opening; retro-aldol and other reactions can then occur, enabling irreversible alkylation.

Funder

Wellcome Trust

Biotechnology and Biological Sciences Research Council

Publisher

Royal Society of Chemistry (RSC)

Subject

Materials Chemistry,Metals and Alloys,Surfaces, Coatings and Films,General Chemistry,Ceramics and Composites,Electronic, Optical and Magnetic Materials,Catalysis

Link

http://pubs.rsc.org/en/content/articlepdf/2023/CC/D3CC02932H

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