Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 10851-10860 |
| Journal | Angewandte Chemie |
| Volume | 133 |
| Issue number | 19 |
| Early online date | 26 Mar 2021 |
| DOIs | |
| Publication status | Published - 3 May 2021 |
Access to Document
- manuscript ACIE 26022021
This is the peer reviewed version of the following article: Guo, Y. et al., 2021. Two‐Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence. Angewandte Chemie., which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1002/ange.202101278. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.