Crocker, Leander B. and Arafiles, Jan Vincent V. and Muchler, Judith M. and Ruwolt, Max and Kemnitz-Hassanin, Kristin and Rossmann, Kilian and Stieger, Christian E. and Liu, Fan and Archipowa, Nataliya and Kutta, Roger Jan and Hackenberger, Christian P. R. (2025) Energy-transfer photoproximity labelling in live cells using an organic cofactor. NATURE CHEMISTRY, 17 (12). pp. 1928-1940. ISSN 1755-4330, 1755-4349
Full text not available from this repository. (Request a copy)Abstract
Photocatalytic proximity labelling has emerged as a powerful tool to resolve a variety of biomolecular and cellular interactions. Although the use of high-resolution probes, such as diazirines, enables cell-surface protein labelling with nanometre precision, intracellular applications are limited by either the intrinsic toxicity of metal-based photocatalysts or by the lower resolution when long-lived reactive intermediates are used. Here we describe the discovery, characterization and application of an organic flavin cofactor derivative, deazaflavin, that activates diazirine to generate carbenes via triplet energy transfer and offers excellent biocompatibility. We demonstrate deazaflavin-diazirine energy-transfer labelling (DarT labelling) for cell surfaceome mapping and, most importantly, for intracellular interactome mapping as exemplified for cell-penetrating peptides. We successfully map the localization of linear and cyclic polyarginine cell-penetrating peptides, identifying putative membrane interactors. Furthermore, we show the applicability of DarT labelling over an extended time period by mapping the intracellular trafficking of a stable cyclic derivative to reveal its eventual exocytosis from the cell. We anticipate that DarT labelling could be used to profile intracellular dynamics across diverse biological systems with high spatio-temporal control.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | 2+2 PHOTOCYCLOADDITION REACTIONS; SINGLET OXYGEN; VISIBLE-LIGHT; PEPTIDE; IDENTIFICATION; REDUCTION; MECHANISM; FLAVINS; BIOLOGY |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 24 Jun 2026 06:14 |
| Last Modified: | 24 Jun 2026 06:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/66420 |
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