The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition

Ray, Sneha; Kreitler, Dale F.; Gulick, Andrew M.; Murkin, Andrew S.

doi:10.1021/acschembio.8b00225

Title: The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition

Journal Article · Mon May 21 00:00:00 UTC 2018 · ACS Chemical Biology

DOI: https://doi.org/10.1021/acschembio.8b00225 · OSTI ID:1502217

Ray, Sneha ^[1]; Kreitler, Dale F. ^[1];

^[1];

^[1]

Univ. at Buffalo, NY (United States)

We report the unprecedented reaction between a nitroalkane and an active-site cysteine residue to yield a thiohydroximate adduct. Structural and kinetic evidence suggests the nitro group is activated by conversion to its nitronic acid tautomer within the active site. Here, the nitro group, therefore, shows promise as a masked electrophile in the design of covalent inhibitors targeting binding pockets with appropriately placed cysteine and general acid residues.

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Research Organization:: Argonne National Laboratory (ANL), Argonne, IL (United States)

Sponsoring Organization:: NIH; NSF

OSTI ID:: 1502217

Journal Information:: ACS Chemical Biology, Journal Name: ACS Chemical Biology Journal Issue: 6 Vol. 13; ISSN 1554-8929

Publisher:: American Chemical Society (ACS)Copyright Statement

Country of Publication:: United States

Language:: ENGLISH

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Cited By (1)

Selective covalent targeting of GPX4 using masked nitrile-oxide electrophiles Eaton, John K.; Furst, Laura; Ruberto, Richard A. Nature Chemical Biology, Vol. 16, Issue 5 https://doi.org/10.1038/s41589-020-0501-5	journal	March 2020

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Title: The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition

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