Discovery of a novel calcium-sensitive fluorescent probe for alpha-ketoglutarate

doi:10.1038/aps.2017.75

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	Discovery of a novel calcium-sensitive fluorescent probe for alpha-ketoglutarate
	Gan, Lin-lin 1,2; Chen, Lin-hai1,2 ; Nan, Fa-jun1,2
刊名	ACTA PHARMACOLOGICA SINICA
	2017-12
卷号	38 期号:12 页码:1683-1690
关键词	nonalcoholic fatty liver disease biomarker alpha-ketoglutarate fluorescent probe calcium-sensitive benzothiazole-coumarin
ISSN号	1671-4083
DOI	10.1038/aps.2017.75
文献子类	Article
英文摘要	alpha-Ketoglutarate (alpha-KG), a pivotal metabolite in energy metabolism, has been implicated in nonalcoholic fatty liver disease (NAFLD) and several cancers. It is recently proposed that plasma alpha-KG is a surrogate biomarker of NAFLD. Here, we report the development of a novel "turn-on" chemosensor for alpha-KG that contains a coumarin moiety as a fluorophore. Using benzothiazole-coumarin (BTC) as inspiration, we designed a probe for calcium ion recognition that possesses a unique fluorophore compared with previously reported probes for alpha-KG measurement. This chemosensor is based on the specific Schiff base reaction and the calcium ion recognition property of the widely used calcium indicator BTC. The probe was synthesized, and a series of parallel experiments were conducted to optimize the chemical recognition process. Compared to the initial weak fluorescence, a remarkable 7.6-fold enhancement in fluorescence intensity (I/I0 at 495 nm) was observed for the conditions in which the probe (1 aemol/L), alpha-KG (50 mu mol/L), and Ca2+ (100 aemol/L) were incubated at 30(1/4)C in EtOH. The probe displayed good selectivity for alpha-KG even in an environment with an abundance of amino acids and other interfering species such as glutaric acid. We determined that the quantitative detection range of alpha-KG in EtOH was between 5 and 50 mu mol/L. Finally, probe in serum loaded with alpha-KG (10 mmol/L) showed a 7.4-fold fluorescence enhancement. In summary, a novel probe for detecting the biomarker alpha-KG through a typical Schiff base reaction has been discovered. With further optimization, this probe may be a good alternative for detecting the physiological metabolite alpha-KG.
WOS关键词	MASS-SPECTROMETRY ; IDH MUTATIONS ; LIQUID ; CELLS
WOS研究方向	Chemistry ; Pharmacology & Pharmacy
语种	英语
CSCD记录号	CSCD:6136217
出版者	ACTA PHARMACOLOGICA SINICA
WOS记录号	WOS:000416938000010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/272371]
专题	国家新药筛选中心中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Nan, Fa-jun
作者单位	1.Univ Chinese Acad Sci, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Chinese Natl Ctr Drug Screening, Shanghai 201203, Peoples R China;
推荐引用方式 GB/T 7714	Gan, Lin-lin,Chen, Lin-hai,Nan, Fa-jun. Discovery of a novel calcium-sensitive fluorescent probe for alpha-ketoglutarate[J]. ACTA PHARMACOLOGICA SINICA,2017,38(12):1683-1690.
APA	Gan, Lin-lin,Chen, Lin-hai,&Nan, Fa-jun.(2017).Discovery of a novel calcium-sensitive fluorescent probe for alpha-ketoglutarate.ACTA PHARMACOLOGICA SINICA,38(12),1683-1690.
MLA	Gan, Lin-lin,et al."Discovery of a novel calcium-sensitive fluorescent probe for alpha-ketoglutarate".ACTA PHARMACOLOGICA SINICA 38.12(2017):1683-1690.