Small-molecule binding-site discovery using silyl ether-enabled chemoproteomics
Keriann M. Backus
Nature Chemistry, Published online: 27 April 2026; doi:10.1038/s41557-026-02127-4 Mapping binding sites using photoaffinity labelling (PAL) is highly valuable but challenging for probe and drug discovery campaigns. Now a chemoproteomic approach has been developed that incorporates cleavable silyl ether linkages into PAL probes to pinpoint and quantify the precise sites where small molecules engage protein binding partners.