Two-Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence.
Angew Chem Int Ed Engl
; 60(19): 10756-10765, 2021 05 03.
Article
em En
| MEDLINE
| ID: mdl-33624914
ABSTRACT
The tracking of cellular senescence usually depends on the detection of senescence-associated ß-galactosidase (SA-ß-gal). Previous probes for SA-ß-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 ß-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-ß-gal from cancer-associated ß-gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme E. coli ß-gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition.
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Base de dados:
MEDLINE
Assunto principal:
Beta-Galactosidase
/
Corantes Fluorescentes
Idioma:
En
Ano de publicação:
2021
Tipo de documento:
Article