K follows C in chemoproteomics
Chemoproteomic mapping of druggable lysines in the proteome
A year after publishing a map of druggable cysteines in the proteome, Ben Cravatt’s lab at Scripps has reported its chemoproteomics tools can also profile lysines. By identifying reactive lysines in dozens of proteins for which no chemical probes exist, let alone candidate molecules, the group continues to expand the universe of druggable targets.
Chemoproteomics was largely pioneered by Cravatt, a professor of chemical physiology at The Scripps Research Institute who has developed a range of chemical tools for identifying specific types of reactive sites on proteins.
Cravatt has founded three drug discovery companies based on the tools: ActivX Biosciences Inc., now a subsidiary of Kyorin Pharmaceutical Co. Ltd., Abide Therapeutics Inc. and Vividion Therapeutics Inc.
The idea is to use chemical fragments to covalently bind and tag a reactive target site, then recover labeled proteins and identify them using mass spectrometry. Cravatt’s team has shown the technology can work in cell extracts and living tissues (see “Ligating Lysines”).
Figure: Ligating lysines
In a Nature Chemistry paper published in July, researchers at The Scripps Research Institute used chemoproteomics to identify reactive lysines in the proteome that could be druggable.
The approach takes advantage of the nucleophilic properties of certain amino acids to fish them out of cell lysates via covalent interactions with electrophilic probe molecules, typically compound fragments.
In the study, the group treated human cell lysates with an