摘要
a-Ketoglutaric acid(a-KA) is an important metabolic intermediate in tricarboxylic acid circle in our body.The mutations of isocitrate dehydrogenase-1(IDH1) and isocitrate dehydrogenase-2(IDH2), however,will lead to the transformation of a-KA into 2-hydroxyglutarate(2-HG), which is confirmed to closely related to actue myeloid leukemia(AML). Therefore it is of great significance to detect a-KA level changes in serum. In this paper, a fluorescent "off-on" probe CH for a-KA was designed based on naphthalimide fluorophore by introducing a hydrazine group for a-KA recognition and a long alkyl amino chain to enhance PET efficiency and water solubility. Cetyltrimethyl ammonium bromide(CTAB) was added toform self-assembly micelles for accelerating the recognition process. CH shows a 28-fold fluorescence enhancement((I - I_0)/I_0 at 550 nm) over other biological species by optimizing the chemical recognition process of CH with a-KA. Significantly, CH was successfully applied for thefluorescence discrimination of all kinds of blood cancer serum samples. This work would provide a potential method that is quick and convenient for sensing a-KA and may promote fluorescence detection in clinical diagnosis.
a-Ketoglutaric acid(a-KA) is an important metabolic intermediate in tricarboxylic acid circle in our body.The mutations of isocitrate dehydrogenase-1(IDH1) and isocitrate dehydrogenase-2(IDH2), however,will lead to the transformation of a-KA into 2-hydroxyglutarate(2-HG), which is confirmed to closely related to actue myeloid leukemia(AML). Therefore it is of great significance to detect a-KA level changes in serum. In this paper, a fluorescent "off-on" probe CH for a-KA was designed based on naphthalimide fluorophore by introducing a hydrazine group for a-KA recognition and a long alkyl amino chain to enhance PET efficiency and water solubility. Cetyltrimethyl ammonium bromide(CTAB) was added toform self-assembly micelles for accelerating the recognition process. CH shows a 28-fold fluorescence enhancement((I - I_0)/I_0 at 550 nm) over other biological species by optimizing the chemical recognition process of CH with a-KA. Significantly, CH was successfully applied for thefluorescence discrimination of all kinds of blood cancer serum samples. This work would provide a potential method that is quick and convenient for sensing a-KA and may promote fluorescence detection in clinical diagnosis.
基金
supported by the National Natural Science Foundation of China (Nos. 21576037, 21422601, 21406028, 21421005)
NSFC-Liaoning United Fund (No. U1608222)