Repurposing Copper(II)/THPTA as A Bioorthogonal Catalyst for Thiazolidine Bond Cleavage
Abstract Metal‐mediated chemical transformations are promising approaches to manipulate and regulate proteins in fundamental biological research and therapeutic development. Nevertheless, unlike bond‐forming reactions, the exploration of selective bond cleavage reactions catalyzed by metals that are...
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Wiley
2024-11-01
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| Series: | Advanced Science |
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| Online Access: | https://doi.org/10.1002/advs.202408180 |
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| author | Chengyun Ma Guoqing Liu Juan Yin Jianan Sun Disheng Luo Dechun Yang Shuo Pang Wei Hou Xinya Hemu Bangce Ye Xiaobao Bi |
| author_facet | Chengyun Ma Guoqing Liu Juan Yin Jianan Sun Disheng Luo Dechun Yang Shuo Pang Wei Hou Xinya Hemu Bangce Ye Xiaobao Bi |
| author_sort | Chengyun Ma |
| collection | DOAJ |
| description | Abstract Metal‐mediated chemical transformations are promising approaches to manipulate and regulate proteins in fundamental biological research and therapeutic development. Nevertheless, unlike bond‐forming reactions, the exploration of selective bond cleavage reactions catalyzed by metals that are fully compatible with proteins and living systems remains relatively limited. Here, it is reported that Copper(II)/tris(3‐hydroxypropyltriazolylmethyl)amine (THPTA), commonly used in copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) reaction, can be repurposed as a new bioorthogonal catalyst for thiazolidine (Thz) bond cleavage. This process liberates an α‐oxo‐aldehyde group under physiological conditions, without requiring additional additives. To showcase the utility of this method, this simple catalyst system is coupled with genetic code expansion technology to achieve on‐demand activation of genetically encoded Thz‐caged α‐oxo‐aldehydes, enabling further functionalization of proteins. For the first time, this cell‐compatible Thz uncaging reaction allows for the site‐specific installation of α‐oxo‐aldehydes at the internal positions of proteins in phage and bacterial surface display systems, expanding the chemical space of proteins. Overall, this study expands the toolkit of bioorthogonal catalysts and paves the way for metal‐promoted chemical reactions in living systems, potentially benefiting various applications in the future. |
| format | Article |
| id | doaj-art-dda7f79dc3e743c4bb1476bccc654df6 |
| institution | Kabale University |
| issn | 2198-3844 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj-art-dda7f79dc3e743c4bb1476bccc654df62025-08-20T03:52:43ZengWileyAdvanced Science2198-38442024-11-011142n/an/a10.1002/advs.202408180Repurposing Copper(II)/THPTA as A Bioorthogonal Catalyst for Thiazolidine Bond CleavageChengyun Ma0Guoqing Liu1Juan Yin2Jianan Sun3Disheng Luo4Dechun Yang5Shuo Pang6Wei Hou7Xinya Hemu8Bangce Ye9Xiaobao Bi10Collaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology Hangzhou 310014 ChinaCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology Hangzhou 310014 ChinaZhejiang Yangshengtang Institute of Natural Medication Co., Ltd Hangzhou 310013 ChinaCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology Hangzhou 310014 ChinaCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology Hangzhou 310014 ChinaCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology Hangzhou 310014 ChinaSchool of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 210009 ChinaCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology Hangzhou 310014 ChinaSchool of Traditional Chinese Pharmacy China Pharmaceutical University Nanjing 210009 ChinaLab of Biosystem and Microanalysis, State Key Laboratory of Bioreactor Engineering East China University of Science and Technology Shanghai 200237 ChinaCollaborative Innovation Center of Yangtze River Delta Region Green Pharmaceuticals, College of Pharmaceutical Sciences Zhejiang University of Technology Hangzhou 310014 ChinaAbstract Metal‐mediated chemical transformations are promising approaches to manipulate and regulate proteins in fundamental biological research and therapeutic development. Nevertheless, unlike bond‐forming reactions, the exploration of selective bond cleavage reactions catalyzed by metals that are fully compatible with proteins and living systems remains relatively limited. Here, it is reported that Copper(II)/tris(3‐hydroxypropyltriazolylmethyl)amine (THPTA), commonly used in copper‐catalyzed azide‐alkyne cycloaddition (CuAAC) reaction, can be repurposed as a new bioorthogonal catalyst for thiazolidine (Thz) bond cleavage. This process liberates an α‐oxo‐aldehyde group under physiological conditions, without requiring additional additives. To showcase the utility of this method, this simple catalyst system is coupled with genetic code expansion technology to achieve on‐demand activation of genetically encoded Thz‐caged α‐oxo‐aldehydes, enabling further functionalization of proteins. For the first time, this cell‐compatible Thz uncaging reaction allows for the site‐specific installation of α‐oxo‐aldehydes at the internal positions of proteins in phage and bacterial surface display systems, expanding the chemical space of proteins. Overall, this study expands the toolkit of bioorthogonal catalysts and paves the way for metal‐promoted chemical reactions in living systems, potentially benefiting various applications in the future.https://doi.org/10.1002/advs.202408180bioorthogonal catalystsbond cleavage reactionscopper ionsliving systemsmetalsthiazolidines |
| spellingShingle | Chengyun Ma Guoqing Liu Juan Yin Jianan Sun Disheng Luo Dechun Yang Shuo Pang Wei Hou Xinya Hemu Bangce Ye Xiaobao Bi Repurposing Copper(II)/THPTA as A Bioorthogonal Catalyst for Thiazolidine Bond Cleavage Advanced Science bioorthogonal catalysts bond cleavage reactions copper ions living systems metals thiazolidines |
| title | Repurposing Copper(II)/THPTA as A Bioorthogonal Catalyst for Thiazolidine Bond Cleavage |
| title_full | Repurposing Copper(II)/THPTA as A Bioorthogonal Catalyst for Thiazolidine Bond Cleavage |
| title_fullStr | Repurposing Copper(II)/THPTA as A Bioorthogonal Catalyst for Thiazolidine Bond Cleavage |
| title_full_unstemmed | Repurposing Copper(II)/THPTA as A Bioorthogonal Catalyst for Thiazolidine Bond Cleavage |
| title_short | Repurposing Copper(II)/THPTA as A Bioorthogonal Catalyst for Thiazolidine Bond Cleavage |
| title_sort | repurposing copper ii thpta as a bioorthogonal catalyst for thiazolidine bond cleavage |
| topic | bioorthogonal catalysts bond cleavage reactions copper ions living systems metals thiazolidines |
| url | https://doi.org/10.1002/advs.202408180 |
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