Carbocation-Based Proximity Labeling
Year: 2026
Type: preprint
Abstract: Photocatalytic proximity labeling platforms use localized release of reactive species to covalently label proteins near a photocatalyst, facilitating the identification of protein interactions. Singlet oxygen, Michael acceptors, radicals, nitrenes, and carbenes are currently used for labeling, with spatial resolution dictated by reactive intermediate lifetime and signal to noise limited by non-catalyzed reactivity. Here, we report a high-resolution proximity labeling platform based on photocatalytic generation of benzylic carbocations from coumarin precursors. Carbocations combine promiscuous crosslinking with limited diffusion in water (t 1/2 < 3 ns) and low non-catalyzed background labeling, properties that enable demanding applications such as small molecule target identification, binding affinity profiling, and proteinprotein interaction discovery on cell surfaces. We show that coumarin-based reagents can be used for improved identification of labeled proteins while maintaining compatibility with commonly used photocatalysts and light setups, allowing them to be used as drop-in replacements for diazirines in existing workflows.
Source: ChemRxiv
Language: English
Topic: Biotin and Related Studies
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7162514338