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Harnessing BODIPY Carbocation Intermediate for Rapid Protein Proximity Modification

ABSTRACT: The attractive photo-decaging chemistries of boron-dipyrromethene (BODIPY) chromophores have been well-established with diverse photochemical applications. This work, however, discovers that meso-substituted BODIPY chromophores can modify proteins in proximity via photo-decaging into hyper-reactive carbocation. Structural modulations of BODIPY photocages accelerate protein labeling kinetics up to 40-fold with t1/2 = 34.6 s. The BODIPY photocage preferentially labels cysteine, lysine and other nucleophilic amino acids via carbocation but not radical intermediate. At low concentration, the BODIPY-mediated labeling reaction only occurs in proximity to proteins due to aqueous quenching of the hyper-reactive carbocation intermediate, resulting in spatially-confined labeling selectivity. When grafted to mitochondria-guiding triphenylphosphine, the BODIPY-PPh3 probe enables stable covalent imaging of depolarized mitochondria, which lose membrane potential to absorb classical non-covalent mitochondria tracers. Harnessing its inherent lipid droplet (LD)-targeting property, the BODIPY-LD probe with an alkyne enrichment handle captures and profiles the dynamic LD interacting proteome in living cells, revealing RTN4 as a LD regulator. Together, the previously overlooked carbocation intermediates of fluorescent photocages (BODIPY, coumarin & cyanine etc.) may expand the toolbox of proximity labeling technologies for spatiotemporal imaging and proteomic analyses.

ORGANISM(S): Mus Musculus

SUBMITTER: Lihua Zhang

PROVIDER: PXD080664 | iProX | Tue Jul 07 00:00:00 GMT+01:00 2026

REPOSITORIES: iProX

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