文献类型：期刊文献

英文题名：A general strategy to the intracellular sensing of glycosidases using AIE-based glycoclusters

作者：Dong, Lei[1,2,3];Zhang, Min-Yu[1,2];Han, Hai-Hao[1,2];Zang, Yi[4];Chen, Guo-Rong[1,2];Li, Jia[4];He, Xiao-Peng[1,2];Vidal, Sebastien[3,5]

机构：[1]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Frontiers Ctr Materiobiol & Dynam Chem, Key Lab Adv Mat,Sch Chem & Mol Engn, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]East China Univ Sci & Technol, Feringa Nobel Prize Scientist Joint Res Ctr, Frontiers Ctr Materiobiol & Dynam Chem, Joint Int Res Lab Precis Chem & Mol Engn,Sch Chem, 130 Meilong Rd, Shanghai 200237, Peoples R China;[3]Univ Lyon, Univ Claude Bernard Lyon 1, Inst Chim & Biochim Mol & Supramol, Lab Chim Organ Glycochim 2,UMR 5246,CNRS, 1 Rue Victor Grignard, F-69622 Villeurbanne, France;[4]Chinese Acad Sci, Natl Ctr Drug Screening, Shanghai Inst Mat Med, State Key Lab Drug Res, 189 Guo Shoujing Rd, Shanghai 201203, Peoples R China;[5]Univ Paris Saclay, Inst Chim Subst Nat, CNRS, UPR 2301, F-91198 Gif Sur Yvette, France

年份：2021

卷号：13

期号：1

起止页码：247

外文期刊名：CHEMICAL SCIENCE

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000729462500001)】；

基金：S. V. thank the Universite Claude Bernard Lyon 1 and the CNRS for financial support. The authors at ECUST are grateful to the financial support from the Natural Science Foundation of China (No. 21788102, 91853201 and 22107029), the Shanghai Municipal Science and Technology Major Project (No. 2018SHZDZX03) and the Fundamental Research Funds for the Central Universities (222201717003). L. D. thanks the China Scholarship Council for a PhD stipend (No. 201606740066). H.-H. H. would like to thank the Project funded by China Postdoctoral Science Foundation (No. 2020M681196). The authors are grateful to Fengming Liu, Yao Li, and Yang Yu of the Integrated Laser Microscopy System at the National Facility for Protein Science in Shanghai (NFPS), Zhangjiang Lab, SARI, China for their help in data collection.

语种：英文

摘要：Glycosidases, which are the enzymes responsible for the removal of residual monosaccharides from glycoconjugates, are involved in many different biological and pathological events. The ability to detect sensitively the activity and spatiotemporal distribution of glycosidases in cells will provide useful tools for disease diagnosis. However, the currently developed fluorogenic probes for glycosidases are generally based on the glycosylation of the phenol group of a donor-acceptor type fluorogen. This molecular scaffold has potential drawbacks in terms of substrate scope, sensitivity because of aggregation-caused quenching (ACQ), and the inability for long-term cell tracking. Here, we developed glycoclusters characterized by aggregation-induced emission (AIE) properties as a general platform for the sensing of a variety of glycosidases. To overcome the low chemical reactivity associated with phenol glycosylation, here we developed an AIE-based scaffold, which is composed of tetraphenylethylene conjugated with dicyanomethylene-4H-pyran (TPE-DCM) with a red fluorescence emission. Subsequently, a pair of dendritic linkages was introduced to both sides of the fluorophore, to which six copies of monosaccharides (d-glucose, d-galactose or l-fucose) were introduced through azide-alkyne click chemistry. The resulting AIE-active glycoclusters were shown to be capable of (1) fluorogenic sensing of a diverse range of glycosidases including beta-d-galactosidase, beta-d-glucosidase and alpha-l-fucosidase through the AIE mechanism, (2) fluorescence imaging of the endogenous glycosidase activities in healthy and cancer cells, and during cell senescence, and (3) glycosidase-activated, long-term imaging of cells. The present study provides a general strategy to the functional, in situ imaging of glycosidase activities through the multivalent display of sugar epitopes of interest onto properly designed AIE-active fluorogens.