文献类型：期刊文献

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

作者：Gao, Ying[1];Hu, Yulu[1];Liu, Qimeng[1];Li, Xiaokang[2];Li, Xinming[2];Kim, Chu-Young[3];James, Tony D.[4];Li, Jian[2,5];Chen, Xi[1];Guo, Yuan[1]

机构：[1]Northwest Univ, Coll Chem & Mat Sci, Minist Educ, Key Lab Synthet & Nat Funct Mol, Xian 710127, Peoples R China;[2]East China Univ Sci & Technol, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Sch Pharm, Shanghai 200237, Peoples R China;[3]Univ Texas El Paso, Dept Chem & Biochem, El Paso, TX 79968 USA;[4]Univ Bath, Dept Chem, Bath BA2 7AY, Avon, England;[5]Tongji Univ, Sch Med, Shanghai Peoples Hosp 10, Clin Med Sci & Tech Innovat Ctr, Shanghai 200092, Peoples R China

年份：2021

卷号：60

期号：19

起止页码：10756

外文期刊名：ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

收录：;EI(收录号：20211310143809);WOS:【SCI-EXPANDED(收录号:WOS:000632952100001)】；

基金：We appreciate the gift of the plasmid containing the sumo-tag from Prof. Shu Quan. We thank the staffs from BL17B/BL18U1 beamline of National Facility for Protein Science in Shanghai (NFPS) at Shanghai Synchrotron Radiation Facility, for assistance during data collection. We thank the experimental facility and the technical services provided by the Synchrotron Radiation Protein Crystallography Facility of the Taiwan Core Facility Program for Biotechnology, and the Taiwan Synchrotron Radiation Research Center. We gratefully acknowledge the financial support from the NSF of China (22037002, 21977082, 21472148 and 21807088), the Natural Science Basic Research Plan for Distinguished Young Scholars in Shaanxi Province of China (2020JC-38) and the Technology Plan Project of Xi'an (GXYD18.1). TDJ wishes to thank the Royal Society for a Wolfson Research Merit Award. YG thanks the University of Orleans in France for the invited professor position.

语种：英文

外文关键词：bioimaging; fluorescent probes; lysosomal pH; senescence; β -galactosidase

摘要：The tracking of cellular senescence usually depends on the detection of senescence-associated beta-galactosidase (SA-beta-gal). Previous probes for SA-beta-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 beta-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-beta-gal from cancer-associated beta-gal, which enables them to track cellular senescence as well as tissue aging more precisely. Our crystal structures of a model enzyme E. coli beta-gal mutant (E537Q) complexed with each probe further revealed the structural basis for probe recognition.