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Isoindolium-Based Allenes: Reactivity Studies and Applications in Fluorescence Temperature Sensing and Cysteine Bioconjugation |
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| Authors: | Wa-Yi O Dr. Jian-Fang Cui Dr. Qiong Yu Dr. Karen Ka-Yan Kung Dr. Sai-Fung Chung Prof. Yun-Chung Leung Prof. Man-Kin Wong |
| Affiliation: | 1. State Key Laboratory of Chemical Biology and Drug Discovery, Research Institute for Future Food, Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518057 China These authors contributed equally to this work.;2. Department of Chemistry, Southern University of Science and Technology, 1088 Xueyuan Blvd., Shenzhen, 518055 China;3. The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518057 China;4. State Key Laboratory of Chemical Biology and Drug Discovery, Research Institute for Future Food, Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China The Hong Kong Polytechnic University Shenzhen Research Institute, Shenzhen, 518057 China;5. Henry Cheng Research Laboratory for Drug Development, Lo Ka Chung Centre for Natural Anti-Cancer Drug Development, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China;6. State Key Laboratory of Chemical Biology and Drug Discovery, Research Institute for Future Food, Department of Food Science and Nutrition, The Hong Kong Polytechnic University, Hung Hom, Hong Kong, China |
| Abstract: | The reaction of a series of electron-deficient isoindolium-based allenes with sulfhydryl compounds has been studied, leading to the formation of isoindolium-based vinyl sulfides. The vinyl sulfides generated could be readily converted into the corresponding indanones and amines upon heating at 30–70 °C with good yields up to 61 %. The thermal cleavage reaction of vinyl sulfides was further studied for developing temperature-sensitive systems. Notably, a novel FRET-based fluorescent temperature sensor was designed and synthesized for temperature sensing at 50 °C, giving a 6.5-fold blue fluorescence enhancement. Moreover, chemoselective bioconjugation of cysteine-containing peptides with the isoindolium-based allenes for the construction of multifunctional peptide bioconjugates was investigated. Thermal cleavage of isoindoliums on the modified peptides at 35–70 °C gave indanone bioconjugates with up to >99 % conversion. These results indicated the biocompatibility of this novel temperature-sensitive reaction. |
| Keywords: | Allenes Chemoselectivity Cysteine FRET Thermal Cleavage Reactions |