Semi-Quantitatively Designing Two-Photon High-Performance Fluorescent Probes for Glutathione S-Transferases
Glutathione S-transferases (GSTs), detoxification enzymes that catalyze the addition of glutathione (GSH) to diverse electrophilic molecules, are often overexpressed in various tumor cells. While fluorescent probes for GSTs have often adopted the 2,4-dinitrobenzenesulfonyl (DNs) group as the recepto...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
American Association for the Advancement of Science (AAAS)
2020-01-01
|
| Series: | Research |
| Online Access: | http://dx.doi.org/10.34133/2020/7043124 |
| _version_ | 1797281039343681536 |
|---|---|
| author | Xue-Xiang Zhang Huan Qi Mei-Heng Lu Song-Qiu Yang Peng Li Hai-long Piao Ke-Li Han |
| author_facet | Xue-Xiang Zhang Huan Qi Mei-Heng Lu Song-Qiu Yang Peng Li Hai-long Piao Ke-Li Han |
| author_sort | Xue-Xiang Zhang |
| collection | DOAJ |
| description | Glutathione S-transferases (GSTs), detoxification enzymes that catalyze the addition of glutathione (GSH) to diverse electrophilic molecules, are often overexpressed in various tumor cells. While fluorescent probes for GSTs have often adopted the 2,4-dinitrobenzenesulfonyl (DNs) group as the receptor unit, they usually suffer from considerable background reaction noise with GSH due to excessive electron deficiency. However, weakening this reactivity is generally accompanied by loss of sensitivity for GSTs, and therefore, finely turning down the reactivity while maintaining certain sensitivity is critical for developing a practical probe. Here, we report a rational semiquantitative strategy for designing such a practical two-photon probe by introducing a parameter adopted from the conceptual density functional theory (CDFT), the local electrophilicity ωk, to characterize this reactivity. As expected, kinetic studies established ωk as efficient to predict the reactivity with GSH, and probe NI3 showing the best performance was successfully applied to detecting GST activities in live cells and tissue sections with high sensitivity and signal-to-noise ratio. Photoinduced electron transfer of naphthalimide-based probes, captured by femtosecond transient absorption for the first time and unraveled by theoretical calculations, also contributes to the negligible background noise. |
| first_indexed | 2024-03-07T16:51:46Z |
| format | Article |
| id | doaj.art-2418dec3ffcb4eea9b994449d3799fba |
| institution | Directory Open Access Journal |
| issn | 2639-5274 |
| language | English |
| last_indexed | 2024-03-07T16:51:46Z |
| publishDate | 2020-01-01 |
| publisher | American Association for the Advancement of Science (AAAS) |
| record_format | Article |
| series | Research |
| spelling | doaj.art-2418dec3ffcb4eea9b994449d3799fba2024-03-03T05:03:45ZengAmerican Association for the Advancement of Science (AAAS)Research2639-52742020-01-01202010.34133/2020/7043124Semi-Quantitatively Designing Two-Photon High-Performance Fluorescent Probes for Glutathione S-TransferasesXue-Xiang Zhang0Huan Qi1Mei-Heng Lu2Song-Qiu Yang3Peng Li4Hai-long Piao5Ke-Li Han6State Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaState Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaState Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaInstitute of Molecular Sciences and Engineering, Shandong University, Qingdao 266237, ChinaCAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, ChinaState Key Laboratory of Molecular Reaction Dynamics, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian 116023, China; Institute of Molecular Sciences and Engineering, Shandong University, Qingdao 266237, ChinaGlutathione S-transferases (GSTs), detoxification enzymes that catalyze the addition of glutathione (GSH) to diverse electrophilic molecules, are often overexpressed in various tumor cells. While fluorescent probes for GSTs have often adopted the 2,4-dinitrobenzenesulfonyl (DNs) group as the receptor unit, they usually suffer from considerable background reaction noise with GSH due to excessive electron deficiency. However, weakening this reactivity is generally accompanied by loss of sensitivity for GSTs, and therefore, finely turning down the reactivity while maintaining certain sensitivity is critical for developing a practical probe. Here, we report a rational semiquantitative strategy for designing such a practical two-photon probe by introducing a parameter adopted from the conceptual density functional theory (CDFT), the local electrophilicity ωk, to characterize this reactivity. As expected, kinetic studies established ωk as efficient to predict the reactivity with GSH, and probe NI3 showing the best performance was successfully applied to detecting GST activities in live cells and tissue sections with high sensitivity and signal-to-noise ratio. Photoinduced electron transfer of naphthalimide-based probes, captured by femtosecond transient absorption for the first time and unraveled by theoretical calculations, also contributes to the negligible background noise.http://dx.doi.org/10.34133/2020/7043124 |
| spellingShingle | Xue-Xiang Zhang Huan Qi Mei-Heng Lu Song-Qiu Yang Peng Li Hai-long Piao Ke-Li Han Semi-Quantitatively Designing Two-Photon High-Performance Fluorescent Probes for Glutathione S-Transferases Research |
| title | Semi-Quantitatively Designing Two-Photon High-Performance Fluorescent Probes for Glutathione S-Transferases |
| title_full | Semi-Quantitatively Designing Two-Photon High-Performance Fluorescent Probes for Glutathione S-Transferases |
| title_fullStr | Semi-Quantitatively Designing Two-Photon High-Performance Fluorescent Probes for Glutathione S-Transferases |
| title_full_unstemmed | Semi-Quantitatively Designing Two-Photon High-Performance Fluorescent Probes for Glutathione S-Transferases |
| title_short | Semi-Quantitatively Designing Two-Photon High-Performance Fluorescent Probes for Glutathione S-Transferases |
| title_sort | semi quantitatively designing two photon high performance fluorescent probes for glutathione s transferases |
| url | http://dx.doi.org/10.34133/2020/7043124 |
| work_keys_str_mv | AT xuexiangzhang semiquantitativelydesigningtwophotonhighperformancefluorescentprobesforglutathionestransferases AT huanqi semiquantitativelydesigningtwophotonhighperformancefluorescentprobesforglutathionestransferases AT meihenglu semiquantitativelydesigningtwophotonhighperformancefluorescentprobesforglutathionestransferases AT songqiuyang semiquantitativelydesigningtwophotonhighperformancefluorescentprobesforglutathionestransferases AT pengli semiquantitativelydesigningtwophotonhighperformancefluorescentprobesforglutathionestransferases AT hailongpiao semiquantitativelydesigningtwophotonhighperformancefluorescentprobesforglutathionestransferases AT kelihan semiquantitativelydesigningtwophotonhighperformancefluorescentprobesforglutathionestransferases |