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Abstract Synthetic fluorescent protein chromophores have been reported for their singlet state fluorescence properties and applications in bioimaging, but rarely for the triplet state chemistries. Herein, we enabled their photo‐sensitizing and photo‐crosslinking properties through rational modulations. Extension of molecular conjugation and introduction of heavy atoms promoted the generation of reactive oxygen species. Unlike other photosensitizers, these chromophores selectively photo‐crosslinked aggregated proteins and uncovered the interactome profiles. We also exemplified their general applications in chromophore‐assisted light inactivation, photodynamic therapy and photo induced polymerization. Theoretical calculation, pathway analysis and transient absorption spectroscopy provided mechanistic insights for this triplet state chemistry. Overall, this work expands the function and application of synthetic fluorescent protein chromophores by enabling their triplet excited state properties.
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Engineering bromodomains with a photoactive amino acid by engaging ‘Privileged’ tRNA synthetases
Site-specific placement of unnatural amino acids, particularly those responsive to light, offers an elegant approach to control protein function and capture their fleeting ‘interactome’. Herein, we have resurrected 4-(trifluoromethyldiazirinyl)-phenylalanine, an underutilized photo-crosslinker, by introducing several key features including easy synthetic access, site-specific incorporation by ‘privileged’ synthetases and superior crosslinking efficiency, to develop photo-crosslinkable bromodomains suitable for ‘interactome’ profiling.
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- Award ID(s):
- 1817692
- PAR ID:
- 10389346
- Date Published:
- Journal Name:
- Chemical Communications
- Volume:
- 56
- Issue:
- 25
- ISSN:
- 1359-7345
- Page Range / eLocation ID:
- 3641 to 3644
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
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- Free Publicly Accessible Full Text
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Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/c9cc09891g
