Issue 22, 2021

Evaluation of fully-functionalized diazirine tags for chemical proteomic applications

Abstract

The use of photo-affinity reagents for the mapping of noncovalent small molecule–protein interactions has become widespread. Recently, several ‘fully-functionalized’ (FF) chemical tags have been developed wherein a photoactivatable capture group, an enrichment handle, and a functional group for synthetic conjugation to a molecule of interest are integrated into a single modular tag. Diazirine-based FF tags in particular are increasingly employed in chemical proteomic investigations; however, despite routine usage, their relative utility has not been established. Here, we systematically evaluate several diazirine-containing FF tags, including a terminal diazirine analog developed herein, for chemical proteomic investigations. Specifically, we compared the general reactivity of five diazirine tags and assessed their impact on the profiles of various small molecules, including fragments and known inhibitors revealing that such tags can have profound effects on the proteomic profiles of chemical probes. Our findings should be informative for chemical probe design, photo-affinity reagent development, and chemical proteomic investigations.

Graphical abstract: Evaluation of fully-functionalized diazirine tags for chemical proteomic applications

Supplementary files

Article information

Article type
Edge Article
Submitted
08 mar. 2021
Accepted
28 abr. 2021
First published
07 may. 2021
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2021,12, 7839-7847

Evaluation of fully-functionalized diazirine tags for chemical proteomic applications

L. P. Conway, A. M. Jadhav, R. A. Homan, W. Li, J. S. Rubiano, R. Hawkins, R. M. Lawrence and C. G. Parker, Chem. Sci., 2021, 12, 7839 DOI: 10.1039/D1SC01360B

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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