Development of Second-Generation Acyl Silane Photoaffinity Probes for Cellular Chemoproteomic Profiling
Year: 2025
Type: article
Abstract: Deconvolution of the protein targets of hit compounds from phenotypic screens, often conducted in live cells, is critical for understanding mechanism of action and identifying potentially hazardous off-target interactions. While photoaffinity labeling and chemoproteomics are long-established approaches for discovering small-molecule-protein interactions in live cells, there are a relatively small number of photoaffinity labeling strategies that can be applied in intracellular settings. Recently, we reported a novel chemical framework for photoaffinity labeling based on the photo-Brook rearrangement of acyl silanes and demonstrated its ability, when appended to protein-targeting ligands, to label recombinant proteins. Here, we report the application of these probes to live cell photoaffinity workflows, demonstrate their complementarity to current state-of-the-art minimalist diazirine-based photoaffinity probes, and introduce a modular synthetic route to access acyl silane scaffolds with improved labeling properties.
Source: ACS Chemical Biology
Institution: University of California, Berkeley
Language: English
Subfield: Organic Chemistry
Field: Chemistry
Domain: Physical Sciences
Open Access status: green
Awards: Acquisition of a Cryoprobe and Related Accessories for a 600 MHz NMR Spectrometer to Support Health Research Activities at the University of California, Berkeley, MFB: Developing Next-Generation Approaches to Targeted Protein Degradation, G6451195267, G883609949, G9000205671, Tackling Undruggable Cancer Targets using Chemoproteomic Platforms, G94847749
OpenAlex ID: W4415091886