biostudies-literatureFeng HThe Youth Innovation Promotion Association CASInnovation Program of Science and Research from the DICP, CASNational Natural Science Foundation of ChinaDalian Science Foundation for Distinguished Young Scholarse2306950https://www.ebi.ac.uk/biostudies/studies/S-EPMC11095223biostudies-literatureUnknown11(18)Intracellular proteome aggregation is a ubiquitous disease hallmark with its composition associated with pathogenicity. Herein, this work reports on a cell-permeable photosensitizer (P8, Rose Bengal derivative) for selective photo induced proximity labeling and crosslinking of cellular aggregated proteome. Rose Bengal is identified out of common photosensitizer scaffolds for its unique intrinsic binding affinity to various protein aggregates driven by the hydrophobic effect. Further acetylation permeabilizes Rose Bengal to selectively image, label, and crosslink aggregated proteome in live stressed cells. A combination of photo-chemical, tandem mass spectrometry, and protein biochemistry characterizations reveals the complexity in photosensitizing pathways (both Type I & II), modification Advanced science (Weinheim, Baden-Wurttemberg, Germany)A Cell-Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome.PMC11095223223224112207413921725506219910822022RJ04DICP I20224520201842222241022374148Zhao NLiu YHuang YFeng HZhao QLiang ZZhang XZhang LfalseA Cell-Permeable Photosensitizer for Selective Proximity Labeling and Crosslinking of Aggregated Proteome.Intracellular proteome aggregation is a ubiquitous disease hallmark with its composition associated with pathogenicity. Herein, this work reports on a cell-permeable photosensitizer (P8, Rose Bengal derivative) for selective photo induced proximity labeling and crosslinking of cellular aggregated proteome. Rose Bengal is identified out of common photosensitizer scaffolds for its unique intrinsic binding affinity to various protein aggregates driven by the hydrophobic effect. Further acetylation permeabilizes Rose Bengal to selectively image, label, and crosslink aggregated proteome in live stressed cells. A combination of photo-chemical, tandem mass spectrometry, and protein biochemistry characterizations reveals the complexity in photosensitizing pathways (both Type I & II), modification 2024-01-01T00:00:00Z2024 May2026-06-03T04:32:30.001Z2026-04-24T03:09:46.29ZS-EPMC110952233844136510.1002/advs.202306950