Design, synthesis and evaluation of an NLRP3 inhibitor diazirine photoaffinity probe

James R. Hill; Rebecca C. Coll; Kate Schroder; Avril A.B. Robertson

doi:10.1016/j.tetlet.2020.151849

Design, synthesis and evaluation of an NLRP3 inhibitor diazirine photoaffinity probe

James R. Hill^*, Rebecca C. Coll, Kate Schroder, Avril A.B. Robertson

^*Corresponding author for this work

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

8 Citations (Scopus)

124 Downloads (Pure)

Abstract

The NLRP3 inhibitor MCC950/CRID3 ameliorates a remarkable number of inflammatory disorders in animal models. Herein we describe a trifluoromethyl phenyl diazirine (TPD) photoaffinity probe, called TPD-950-Br, to probe the molecular interactions of MCC950. We show that TPD-950-Br covalently captures proximal species upon photo-activation and inhibits IL-1β production in an NLRP3 inhibitor assay.

Original language	English
Article number	151849
Journal	Tetrahedron Letters
Early online date	16 Mar 2020
DOIs	https://doi.org/10.1016/j.tetlet.2020.151849
Publication status	Early online date - 16 Mar 2020

Keywords

Diazirine
NLRP3 inflammasome
Photoaffinity
Sandmeyer

ASJC Scopus subject areas

Biochemistry
Drug Discovery
Organic Chemistry

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10.1016/j.tetlet.2020.151849Licence: Unspecified

Design, Synthesis and Evaluation of an NLRP3 Inhibitor Diazirine Photoaffinity Probe
Copyright 2020 Elsevier Ltd. This manuscript is distributed under a Creative Commons Attribution-NonCommercial-NoDerivs License (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits distribution and reproduction for non-commercial purposes, provided the author and source are cited.
Accepted author manuscript, 978 KBLicence: CC BY-NC-ND

Cite this

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abstract = "The NLRP3 inhibitor MCC950/CRID3 ameliorates a remarkable number of inflammatory disorders in animal models. Herein we describe a trifluoromethyl phenyl diazirine (TPD) photoaffinity probe, called TPD-950-Br, to probe the molecular interactions of MCC950. We show that TPD-950-Br covalently captures proximal species upon photo-activation and inhibits IL-1β production in an NLRP3 inhibitor assay.",

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AB - The NLRP3 inhibitor MCC950/CRID3 ameliorates a remarkable number of inflammatory disorders in animal models. Herein we describe a trifluoromethyl phenyl diazirine (TPD) photoaffinity probe, called TPD-950-Br, to probe the molecular interactions of MCC950. We show that TPD-950-Br covalently captures proximal species upon photo-activation and inhibits IL-1β production in an NLRP3 inhibitor assay.

KW - Diazirine

KW - NLRP3 inflammasome

KW - Photoaffinity

KW - Sandmeyer

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DO - 10.1016/j.tetlet.2020.151849

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ER -

Design, synthesis and evaluation of an NLRP3 inhibitor diazirine photoaffinity probe

Abstract

Keywords

ASJC Scopus subject areas

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