文献类型：期刊文献

英文题名：First-generation species-selective chemical probes for fluorescence imaging of human senescence-associated β-galactosidase

作者：Li, Xiaokang[1];Qiu, Wenjing[1];Li, Jinwen[1];Chen, Xi[2];Hu, Yulu[2];Gao, Ying[2];Shi, Donglei[1];Li, Xinming[1];Lin, Huiling[1];Hu, Zelan[1];Dong, Guoqiang[3];Sheng, Chunquan[3];Jiang, Bei[4];Xia, Conglong[4];Kim, Chu-Young[5];Guo, Yuan[2];Li, Jian[1,4]

机构：[1]East China Univ Sci & Technol, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai Key Lab New Drug Design, Shanghai 200237, Peoples R China;[2]Northwest Univ, Coll Chem & Mat Sci, Key Lab Synthet & Nat Funct Mol, Minist Educ, Xian 710127, Peoples R China;[3]Second Mil Med Univ, Sch Pharm, Shanghai 200433, Peoples R China;[4]Dali Univ, Inst Mat Med, Coll Pharm & Chem, Dali 671000, Peoples R China;[5]Univ Texas El Paso, Dept Chem & Biochem, El Paso, TX 79968 USA

年份：2020

卷号：11

期号：28

起止页码：7292

外文期刊名：CHEMICAL SCIENCE

收录：;EI(收录号：20203108999045);WOS:【SCI-EXPANDED(收录号:WOS:000550969100028)】；

基金：We appreciate the gi. of the plasmid containing the sumo-tag from Prof. Shu Quan and the gift of 23 month-old C57BL/6J mice from Prof. Yuzheng Zhao. We thank the staff from beam lines BL17B1 and BL18U1 at the Shanghai Synchrotron Radiation Facility for assistance with crystal diffraction 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. This work was supported by the National Key R&D Program of China (2017YFB0202600), the National Natural Science Foundation of China (81872747, 21977082, 81903457, 81872742), the Innovative Research Team of High-level Local Universities in Shanghai, the Natural Science Basic Research Plan for Distinguished Young Scholars in Shaanxi Province of China (No. 2020JC-38), the National Special Fund for State Key Laboratory of Bioreactor Engineering (2060204), the Open Funding Project of the State Key Laboratory of Bioreactor Engineering (2018OPEN12), the Chinese Postdoctoral Science Foundation (2018M641946), the Shanghai Sailing Program (19YF1412600), and the Shanghai Morning Light Program (18CG33).

语种：英文

外文关键词：Probes - Fluorescence imaging - Enzymes - Fluorescence spectroscopy - Mammals

摘要：Human senescence-associated beta-galactosidase (SA-beta-gal), the most widely used biomarker of aging, is a valuable tool for assessing the extent of cell 'healthy aging' and potentially predicting the health life span of an individual. Human SA-beta-gal is an endogenous lysosomal enzyme expressed from GLB1, the catalytic domain of which is very different from that of E. coli beta-gal, a bacterial enzyme encoded by lacZ. However, existing chemical probes for this marker still lack the ability to distinguish human SA-beta-gal from beta-gal of other species, such as bacterial beta-gal, which can yield false positive signals. Here, we show a molecular design strategy to construct fluorescent probes with the above ability with the aid of structure-based steric hindrance adjustment catering to different enzyme pockets. The resulting probes normally work as traditional SA-beta-gal probes, but they are unique in their powerful ability to distinguish human SA-beta-gal from E. coli beta-gal, thus achieving species-selective visualization of human SA-beta-gal for the first time. NIR-emitting fluorescent probe KSL11 as their representative further displays excellent species-selective recognition performance in biological systems, which has been herein verified by testing in senescent cells, in lacZ-transfected cells and in E. coli-beta-gal-contaminated tissue sections of mice. Because of our probes, it was also discovered that SA-beta-gal content in mice increased gradually with age and SA-beta-gal accumulated most in the kidneys among the main organs of naturally aging mice, suggesting that the kidneys are the organs with the most severe aging during natural aging.