Two‐Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence
| Autor: | Yuan Guo, Yulu Hu, Xiaokang Li, Tony D. James, Qimeng Liu, Jian Li, Xi Chen, Chu-Young Kim, Xinming Li, Ying Gao |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Senescence
010405 organic chemistry Chemistry Mutant Cellular senescence Endogeny General Medicine General Chemistry 010402 general chemistry Tracking (particle physics) beta-Galactosidase 01 natural sciences Fluorescence Catalysis 0104 chemical sciences Cell biology SDG 3 - Good Health and Well-being Mutation Escherichia coli Cellular Senescence Fluorescent Dyes |
| Zdroj: | Guo, Y, Gao, Y, Hu, Y, Liu, Q, Li, X, Li, X, Kim, C-Y, James, T D, Li, J & Chen, X 2021, ' Two-Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence ', Angewandte Chemie, vol. 133, no. 19, pp. 10851-10860 . https://doi.org/10.1002/ange.202101278 |
| Popis: | The tracking of cellular senescence usually depends on the detection of senescence‐associated β‐galactosidase (SA‐β‐gal). Previous probes for SA‐β‐gal with this purpose only cover a single dimension: the accumulation of this enzyme in lysosomes. However, this is insufficient to determine the destiny of senescence because endogenous β‐gal enriched in lysosomes is not only related to senescence, but also to some other physiological processes. To address this issue, we introduce our fluorescent probes including a second dimension: lysosomal pH, since de‐acidification is a unique feature of the lysosomes in senescent cells. With this novel design, our probes achieved excellent discrimination of SA‐β‐gal from cancer‐associated β‐gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme E. coli β‐gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition. |
| Databáze: | OpenAIRE |
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