The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition

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

doi:10.1021/acschembio.8b00225

The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition

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

SUNY Buffalo

Research output: Contribution to journal › Article › peer-review

36 Scopus citations

Abstract

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. 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.

Original language	English
Pages (from-to)	1470-1473
Number of pages	4
Journal	ACS Chemical Biology
Volume	13
Issue number	6
DOIs	https://doi.org/10.1021/acschembio.8b00225
State	Published - Jun 15 2018

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title = "The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition",

abstract = "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. 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.",

author = "Sneha Ray and Kreitler, \{Dale F.\} and Gulick, \{Andrew M.\} and Murkin, \{Andrew S.\}",

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AU - Ray, Sneha

AU - Kreitler, Dale F.

AU - Gulick, Andrew M.

AU - Murkin, Andrew S.

PY - 2018/6/15

Y1 - 2018/6/15

N2 - 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. 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.

AB - 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. 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.

UR - https://www.scopus.com/pages/publications/85047486896

U2 - 10.1021/acschembio.8b00225

DO - 10.1021/acschembio.8b00225

M3 - Article

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AN - SCOPUS:85047486896

SN - 1554-8929

VL - 13

SP - 1470

EP - 1473

JO - ACS Chemical Biology

JF - ACS Chemical Biology

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ER -

The Nitro Group as a Masked Electrophile in Covalent Enzyme Inhibition

Abstract

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