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Ketal-Bridged Rhodamines as a New Scaffold for Near-Infrared Chemigenetic Indicators with Enhanced Fluorogenicity
Xu Ding1, Quan Zhang1, Hailin Bai1
1State Key Laboratory of Chemo/Bio-Sensing, College of Chemistry and Chemical Engineering, Hunan University, Changsha, Hunan 410082, China.
Journal of the American Chemical Society
|May 21, 2026
Summary
Researchers developed new near-infrared (NIR) chemigenetic indicators using engineered ketal-bridged rhodamines. These advanced probes offer superior brightness, photostability, and fluorogenicity for enhanced biological imaging and biosensing applications.
Area of Science:
- Biochemistry
- Molecular Biology
- Bioimaging
Background:
- Current chemigenetic indicators have limitations in fluorogenicity, photostability, and synthetic complexity.
- There is a need for advanced probes that combine spectral tunability with genetic encoding for biological imaging.
Purpose of the Study:
- To develop novel near-infrared (NIR) chemigenetic indicators with improved performance.
- To engineer ketal-bridged rhodamines for enhanced bioimaging and biosensing.
Main Methods:
- Engineering ketal-bridged rhodamines for NIR chemigenetic indicators.
- Utilizing a "bridge addition" strategy for facile synthesis.
- Testing indicator performance in live cell imaging and super-resolution microscopy (SIM).
Main Results:
- Ketal-bridged rhodamines exhibit distinct NIR excitation/emission, superior brightness, and enhanced photostability.
- Indicators show high fluorescence activation ratios and fluorogenicity with HaloTag protein.
- Successful imaging of proteins in organelles, RNA, and kinase activity was demonstrated.
Conclusions:
- Ketal-bridged rhodamine-based indicators represent a promising advancement in chemigenetic tools.
- These probes offer improved contrast for bioimaging and biosensing applications.
- The developed scaffold facilitates the creation of new indicators with enhanced properties.
