A versatile fluorescence-quenched substrate for quantitative measurement of glucocerebrosidase activity within live cells was written by Deen, Matthew C.;Zhu, Yanping;Gros, Christina;Na, Na;Gilormini, Pierre-Andre;Shen, David L.;Bhosale, Sandeep;Anastasi, Nadia;Wang, RuiQi;Shan, Xiaoyang;Harde, Eva;Jagasia, Ravi;Lynn, Francis C.;Vocadlo, David J.. And the article was included in Proceedings of the National Academy of Sciences of the United States of America in 2022.COA of Formula: C16H22O11 The following contents are mentioned in the article:
Loss of activity of the lysosomal glycosidase 尾-glucocerebrosidase (GCase) causes the lysosomal storage disease Gaucher disease (GD) and has emerged as the greatest genetic risk factor for the development of both Parkinson disease (PD) and dementia with Lewy bodies. There is significant interest into how GCase dysfunction contributes to these diseases, however, progress toward a full understanding is complicated by presence of endogenous cellular factors that influence lysosomal GCase activity. Indeed, such factors are thought to contribute to the high degree of variable penetrance of GBA mutations among patients. Robust methods to quant. measure GCase activity within lysosomes are therefore needed to advance research in this area, as well as to develop clin. assays to monitor disease progression and assess GCase-directed therapeutics. Here, we report a selective fluorescence-quenched substrate, LysoFQ-GBA, which enables measuring endogenous levels of lysosomal GCase activity within living cells. LysoFQ-GBA is a sensitive tool for studying chem. or genetic perturbations of GCase activity using either fluorescence microscopy or flow cytometry. We validate the quant. nature of measurements made with LysoFQ-GBA using various cell types and demonstrate that it accurately reports on both target engagement by GCase inhibitors and the GBA allele status of cells. Furthermore, through comparisons of GD, PD, and control patient-derived tissues, we show there is a close correlation in the lysosomal GCase activity within monocytes, neuronal progenitor cells, and neurons. Accordingly, anal. of clin. blood samples using LysoFQ-GBA may provide a surrogate marker of lysosomal GCase activity in neuronal tissue. This study involved multiple reactions and reactants, such as (2S,3R,4S,5R,6R)-6-(Acetoxymethyl)tetrahydro-2H-pyran-2,3,4,5-tetrayl tetraacetate (cas: 604-69-3COA of Formula: C16H22O11).
(2S,3R,4S,5R,6R)-6-(Acetoxymethyl)tetrahydro-2H-pyran-2,3,4,5-tetrayl tetraacetate (cas: 604-69-3) belongs to esters. Esters typically have a pleasant smell; those of low molecular weight are commonly used as fragrances and are found in essential oils and pheromones. Many esters have the potential for conformational isomerism, but they tend to adopt an s-cis (or Z) conformation rather than the s-trans (or E) alternative, due to a combination of hyperconjugation and dipole minimization effects. The preference for the Z conformation is influenced by the nature of the substituents and solvent, if present. Lactones with small rings are restricted to the s-trans (i.e. E) conformation due to their cyclic structure.COA of Formula: C16H22O11
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