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]; Zhang, Min-Yu[1]; Han, Hai-Hao[1]; Zang, Yi[3]; Chen, Guo-Rong[1]; Li, Jia[3]; He, Xiao-Peng[1]; Vidal, Sébastien[2,4]

机构：[1] Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, Frontiers Center for Materiobiology and Dynamic Chemistry, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Rd., Shanghai, 200237, China; [2] Institut de Chimie et Biochimie Moléculaires et Supramoléculaires, Laboratoire de Chimie Organique 2-Glycochimie, UMR 5246, CNRS, Université Claude Bernard Lyon 1, Université de Lyon, 1 Rue Victor Grignard, Villeurbanne, F-69622, France; [3] National Centre for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 189 Guo Shoujing Rd., Shanghai, 201203, China; [4] Université Paris-Saclay, CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, Gif-sur-Yvette, 91198, France

年份：2022

卷号：13

期号：1

起止页码：247

外文期刊名：Chemical Science

收录：EI(收录号：20215311407152)

语种：英文

外文关键词：Diagnosis - Cells - Glucose - Fluorescence imaging - Phenols - Cancer cells - Scaffolds (biology) - Cytology

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 orl-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 β-d-galactosidase, β-d-glucosidase and α-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 situimaging of glycosidase activities through the multivalent display of sugar epitopes of interest onto properly designed AIE-active fluorogens. ? The Royal Society of Chemistry 2021.