Bio-orthogonally Activatable Fluorescent Probe for Specific Imaging of Myeloid Cell Leukemia 1 Protein
Yong Li1, Jiangong Zhang1, Xiaolong Ni1
1College of Chemistry, Chemical Engineering and Materials Science, Key Laboratory of Molecular and Nano Probes, Ministry of Education, Collaborative Innovation Center of Functionalized Probes for Chemical Imaging in Universities of Shandong, Institute of Molecular and Nano Science, Shandong Normal University, Jinan 250014, P. R. China.
Abstract:
The antiapoptotic protein myeloid cell leukemia 1 (Mcl-1) has been increasingly identified as a promising potential therapeutic target attributed to its critical regulation effect in diverse cellar physiopathological events. Current fluorescence imaging strategies tend to be susceptible to the cellular microenvironment, and straightforward mapping of Mcl-1's level variation remains challenging. In this paper, an activatable "off-on" fluorescence strategy for Mcl-1 specific labeling was presented based on bio-orthogonal chemistry by introducing tetrazine-functionalized borondipyrromethene (TB) as a fluorescent reporter and trans-cyclooctyne-derived indole-2-carboxylic acid (TI) as an Mcl-1 targeting moiety. With the click pair of TB and TI, the Mcl-1 expression level in vitro and in vivo was successfully mapped straightforward. Also, the level changes of Mcl-1 upon drug challenge were demonstrated. This work provides a robust fluorescence strategy for Mcl-1 in situ imaging, and the results would further facilitate the comprehensive revelation of the Mcl-1 biological effect.
Insights
Researchers developed a novel "off-on" fluorescence imaging strategy to precisely map myeloid cell leukemia 1 (Mcl-1) levels. This method utilizes bio-orthogonal chemistry for accurate Mcl-1 detection in vitro and in vivo, aiding therapeutic target studies.
Area of Science:
- Biochemistry
- Molecular Biology
- Medical Imaging
Background:
- Myeloid cell leukemia 1 (Mcl-1) is a key antiapoptotic protein and a promising therapeutic target.
- Current fluorescence imaging methods for Mcl-1 are limited by environmental interference and mapping challenges.
Purpose of the Study:
- To develop an activatable "off-on" fluorescence strategy for specific Mcl-1 labeling.
- To enable straightforward mapping of Mcl-1 expression levels in vitro and in vivo.
- To demonstrate Mcl-1 level changes in response to drug treatment.
Main Methods:
- Utilized bio-orthogonal chemistry with a tetrazine-functionalized borondipyrromethene (TB) fluorescent reporter.
- Employed a trans-cyclooctyne-derived indole-2-carboxylic acid (TI) as the Mcl-1 targeting moiety.
- Applied the TB-TI click chemistry pair for Mcl-1 detection.
Main Results:
- Successfully mapped Mcl-1 expression levels in vitro and in vivo using the developed strategy.
- Demonstrated the ability to track changes in Mcl-1 levels upon drug challenge.
- Validated the robustness and specificity of the fluorescence imaging approach.
Conclusions:
- The study presents a robust "off-on" fluorescence strategy for Mcl-1 in situ imaging.
- This approach overcomes limitations of current methods, enabling precise Mcl-1 level mapping.
- The findings will advance the understanding of Mcl-1's biological roles and therapeutic potential.
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