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Photoaffinity labeling (PAL) is a powerful technique in chemical biology and chemical proteomics, and has been successfully demonstrated on a variety of non-covalent molecular interactions.[1] Recently, we and others have shown that this approach is suitable for interrogating noncovalent protein–drug interactions under native cellular conditions.[2, 3] To do so, typically the drug is derivatized with a photo-reactive group and a reporter group (referred to herein as the linker), to make the corresponding probe.[2b] Upon administration into live cells and photo-irradiation, a highly reactive intermediate is generated from the probe, which can covalently capture its binding proteins in a distance-dependent manner. The chemically stable, cross-linked protein–probe complexes thus become amenable to various downstream biochemical analyses, including pull-down (PD)/LC-MS/MS analysis, for large-scale identification of …