A general strategy to the intracellular sensing of glycosidases using AIE-based glycoclusters

doi:10.1039/d1sc05057e

	A general strategy to the intracellular sensing of glycosidases using AIE-based glycoclusters
	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
刊名	CHEMICAL SCIENCE
	2021-12-22
卷号	13 期号:1 页码:247-256
ISSN号	2041-6520
DOI	10.1039/d1sc05057e
通讯作者	Li, Jia(jli@simm.ac.cn) ; He, Xiao-Peng(xphe@ecust.edu.cn) ; Vidal, Sebastien(sebastien.vidal@cnrs.fr)
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.
资助项目	Universite Claude Bernard Lyon 1 ; CNRS ; Natural Science Foundation of China[21788102] ; Natural Science Foundation of China[91853201] ; Natural Science Foundation of China[22107029] ; Shanghai Municipal Science and Technology Major Project[2018SHZDZX03] ; Fundamental Research Funds for the Central Universities[222201717003] ; China Scholarship Council[201606740066] ; China Postdoctoral Science Foundation[2020M681196]
WOS关键词	BETA-GALACTOSIDASE ACTIVITY ; ALPHA-L-FUCOSIDASE ; FLUORESCENT-PROBE ; HEPATOCELLULAR-CARCINOMA ; CHEMICAL PROBES ; CLICK CHEMISTRY ; TRACKING ; CELLS ; NANOPARTICLES ; RELEVANT
WOS研究方向	Chemistry
语种	英语
出版者	ROYAL SOC CHEMISTRY
WOS记录号	WOS:000729462500001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/299205]
专题	中国科学院上海药物研究所
通讯作者	Li, Jia; He, Xiao-Peng; Vidal, Sebastien
作者单位	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
推荐引用方式 GB/T 7714	Dong, Lei,Zhang, Min-Yu,Han, Hai-Hao,et al. A general strategy to the intracellular sensing of glycosidases using AIE-based glycoclusters[J]. CHEMICAL SCIENCE,2021,13(1):247-256.
APA	Dong, Lei.,Zhang, Min-Yu.,Han, Hai-Hao.,Zang, Yi.,Chen, Guo-Rong.,...&Vidal, Sebastien.(2021).A general strategy to the intracellular sensing of glycosidases using AIE-based glycoclusters.CHEMICAL SCIENCE,13(1),247-256.
MLA	Dong, Lei,et al."A general strategy to the intracellular sensing of glycosidases using AIE-based glycoclusters".CHEMICAL SCIENCE 13.1(2021):247-256.