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Development of a Chemogenetic Approach to Manipulate Intracellular pH

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JOURNAL OF THE AMERICAN CHEMICAL SOCIETY
卷 145, 期 22, 页码 11899-11902

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AMER CHEMICAL SOC
DOI: 10.1021/jacs.3c00703

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pH-Control is a novel enzymatic method that allows precise control of ultralocal acidification in living cells. The genetically encoded biosensor SypHer3s demonstrated that pH-Control effectively acidifies cytosolic, mitochondrial, and nuclear pH in a concentration-dependent manner. This approach shows promise in investigating the ultralocal pH imbalance associated with various diseases.
Chemogenetic Operation of iNTRacellular prOton Levels(pH-Control)is a novel substrate-based enzymatic method that enables precise spatiotemporalcontrol of ultralocal acidification in cultured cell lines and primaryneurons. The genetically encoded biosensor SypHer3s showed that pH-Controleffectively acidifies cytosolic, mitochondrial, and nuclear pH exclusivelyin the presence of beta-chloro-d-alanine in living cellsin a concentration-dependent manner. The pH-Control approach is promisingfor investigating the ultralocal pH imbalance associated with manydiseases.

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