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.

1 Introduction

2 Structure, Bonding, and Spectral Properties

3 Photoreactivity

4 Synthesis

5 Application in Photoaffinity Labeling

6 Discovery of a Cholesterol–Hedgehog Protein Interface

7 Conclusions and Outlook

Key words

diazirine - carbene - photoreactivity - chemical biology - protein-ligand interactions

Publication History

Received: 28 February 2021

Accepted after revision: 15 March 2021

Accepted Manuscript online:
15 March 2021

Article published online:
09 April 2021

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