2. Academic Validation
  3. Two-Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence

Two-Dimensional Design Strategy to Construct Smart Fluorescent Probes for the Precise Tracking of Senescence

  • Angew Chem Int Ed Engl. 2021 May 3;60(19):10756-10765. doi: 10.1002/anie.202101278.
Ying Gao 1,  Yulu Hu 1,  Qimeng Liu 1,  Xiaokang Li 2,  Xinming Li 2,  Chu-Young Kim 3,  Tony D James 4,  Jian Li 2 5,  Xi Chen 1,  Yuan Guo 1
Affiliations

Affiliations

  • 1 Key Laboratory of Synthetic and Natural Functional Molecule of the Ministry of Education, College of Chemistry and Materials Science, Northwest University, Xi'an, 710127, China.
  • 2 State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, Shanghai, 200237, China.
  • 3 Department of Chemistry and Biochemistry, The University of Texas at El Paso, El Paso, TX, 79968, USA.
  • 4 Department of Chemistry, University of Bath, Bath, BA2 7AY, UK.
  • 5 Clinical Medicine Scientific and Technical Innovation Center, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, 200092, China.
PMID: 33624914 DOI: 10.1002/anie.202101278
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.

Keywords

bioimaging; fluorescent probes; lysosomal pH; senescence; β-galactosidase.

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