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A Photoaffinity Displacement Assay and Probes to Study the Cyclin‐Dependent Kinase Family
Author(s) -
Grant Emma K.,
Fallon David J.,
Eberl H. Christian,
Fantom Ken G. M.,
Zappacosta Francesca,
Messenger Cassie,
Tomkinson Nicholas C. O.,
Bush Jacob T.
Publication year - 2019
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201906321
Subject(s) - cyclin dependent kinase , photoaffinity labeling , kinase , chemistry , small molecule , gene isoform , biochemistry , cell cycle , microbiology and biotechnology , binding site , biology , cell , gene
The CDK family plays a crucial role in the control of the cell cycle. Dysregulation and mutation of the CDKs has been implicated in cancer and the CDKs have been investigated extensively as potential therapeutic targets. Selective inhibition of specific isoforms of the CDKs is crucial to achieve therapeutic effect while minimising toxicity. We present a group of photoaffinity probes designed to bind to the family of CDKs. The site of crosslinking of the optimised probe, as well as its ability to enrich members of the CDK family from cell lysates, was investigated. In a proof of concept study, we subsequently developed a photoaffinity probe‐based competition assay to profile CDK inhibitors. We anticipate that this approach will be widely applicable to the study of small molecule binding to protein families of interest.