Glycosidases, which are the enzymes responsible for removal of residual monosaccharides from glycoconjugates, are involved in many different biological and pathological events. The ability to detect sensitively the activity and...

Glycosidases, which are the enzymes responsible for removal of residual monosaccharides from glycoconjugates, are implicated in a myriad of biological and pathological events. The ability to detect sensitively the activity and spatiotemporal distribution of glycosidases in cells may facilitate the study of glycobiology, and add useful diagnostic tools. However, the currently developed fluorogenic probes for glycosidases are generally based on glycosylation of a phenol group of a donor-acceptor type fluorogen. This general 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 during phenol glycosylation, we synthesized an AIE-based dye 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 different monosaccharides (D-glucose, D-galactose and L-fucose) were conjugated 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 imaging of glycosidase activities through the multivalent display of sugar epitopes of interest onto AIE-active dyes.

BACKGROUND MLL gene rearrangement is a common genetic abnormality of acute myeloid leukemia (AML), which predicts poor prognosis and is important in clinical diagnosis. MLL rearrangement involves many chromosomes, among which, t(4;11) translocation is rare in AML. The present case was t(4;11) AML, accompanied by a hyperdiploid karyotype. Such cases have not been reported previously. CASE SUMMARY An adult male with self-reported symptoms of fatigue, febrility and hyperleukocytosis was diagnosed with AML by morphology and confirmed by immunophenotype analysis. Uncommonly, chromosomal and fluorescence in situ hybridization (FISH) analysis showed a hyperdiploid karyotype with t(4;11) translocation and MLL rearrangement, and a negative MLL – AF4 fusion gene result. The patient died of respiratory and circulatory failure 5 days after diagnosis. CONCLUSION t(4;11) AML with hyperdiploid karyotype has not been reported. In this case, t(4;11) was only detected by karyotype analysis and FISH, suggesting their importance in MLL rearrangement detection.

Glycosidases play important roles in modulating the structural and functional integrity of glycoproteins and glycolipids, and thus are promising biomarkers for disease diagnosis. While current approaches for glycosidase detection mainly...

Glycosidases, which are the enzymes responsible for removal of residual monosaccharides from glycoconjugates, are implicated in a myriad of biological and pathological events. The ability to detect sensitively the activity and spatiotemporal distribution of glycosidases in cells may facilitate the study of glycobiology, and add useful diagnostic tools. However, the currently developed fluorogenic probes for glycosidases are generally based on glycosylation of a phenol group of a donor-acceptor type fluorogen. This general 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 during phenol glycosylation, we synthesized an AIE-based dye 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 different monosaccharides (D-glucose, D-galactose and L-fucose) were conjugated 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 imaging of glycosidase activities through the multivalent display of sugar epitopes of interest onto AIE-active dyes.