Target identification and occupancy measurement of necrosis avid agent rhein using bioorthogonal chemistry-enabling probes |
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| Authors: | Cuihua Jiang Jian Zhang Shihe Hu Meng Gao Dongjian Zhang Nan Yao Qiaomei Jin |
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| Affiliation: | Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing 210028 Jiangsu China.; Laboratories of Translational Medicine, Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028 Jiangsu China |
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| Abstract: | Necrosis is an important biomarker, which only occurs in pathological situations. Tracking of necrosis avid agents is of crucial importance toward understanding their mechanisms. Herein, we developed a modular probe strategy based on bioorthogonal copper-free click chemistry. Structural modification of rhein with transcyclooctene (TCO) led to the identification of rhein-TCO2 as the most active probe with specific necrosis affinity. In a systematic evaluation, the colocalization of rhein-TCO2 in the nucleus (exposed DNA and rRNA) of necrotic cells was observed. This work provides a foundation for the development of target-identified of rhein compounds, and binding to exposed DNA and rRNA may be an important target of rhein compounds in necrotic cells.Structural modification of rhein with transcyclooctene (TCO) led to the identification of rhein-TCO2 as the most active probe with specific necrosis affinity. |
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