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Published July 2021 | Published
Journal Article Open

Structure, Bonding, and Photoaffinity Labeling Applications of Dialkyldiazirines

Abstract

Dialkyldiazirine photoaffinity probes are unparalleled tools for the study of small molecule–protein interactions. Here we summarize the basic principles of structure, bonding, and photoreactivity of dialkyldiazirines, current methods for their synthesis, and their practical application in photoaffinity labeling experiments. We demonstrate the unique utility of dialkyldiazirine probes in the context of our recent photoaffinity crosslinking-mass spectrometry analysis to reveal a hidden cholesterol binding site in the Hedgehog morphogen proteins.

Additional Information

© 2021. This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/). Received: 28 February 2021; Accepted after revision: 15 March 2021; Publication Date: 15 March 2021 (online). We thank Dr. Y.-S. Cheng and Prof. R. G. Hadt for invaluable input during the preparation of this manuscript. Support was provided by Caltech start-up funds for A.E.O. and a John Stauffer Charitable Trust SURF Fellowship for T.Z. California Institute of Technology. The authors declare no conflict of interest.

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Created:
August 20, 2023
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October 23, 2023