新型荧光探针可对Cys和GSH的生物合成进行多色成



本期文章:《美国化学会志》:Online/在线发表

山西大学阴彩霞课题组开发出可对Cys和GSH生物合成进行多色成像的荧光探针。2020年12月24日,《美国化学会志》在线发表了这项成果。

研究人员向共轭乙二胺香豆素和吡喃二酮的α,β-不饱和酮中引入了氟化硼,并通过其强大的电子缺乏效应提供了一种具有近红外发射并调节分子刚性的分子。同时,共轭双键用于响应分子的刚性。探针对生物硫醇的快速响应以及探针自身通过响应环境的缓慢解离聚集可以监测细胞中是否存在生物硫醇。此外,基于Cys和GSH对探针反应的敏感性差异,这项工作首次通过酶抑制研究了细胞中Cys和GSH的生物合成途径之间的相互作用。并揭示了体内生物合成的限制与调节的关系。

据了解,生物合成是维持生命的必要过程。近年来,研究已充分表明,三种生物硫醇(Cys、Hcy、GSH)主要在氧化应激和维持细胞内细胞稳态方面发挥作用,并且浓度异常会导致心血管、癌症等疾病的发生。各种荧光探针在检测其浓度和研究其生物学功能方面显示出空前的优势。实际上,这三种生物硫醇是在体内生物合成过程中产生的。了解它们的生物合成途径并阐明其合成关系具有重要意义。

附:英文原文

Title: Rapid Reaction, Slow Dissociation Aggregation, and Synergetic Multicolor Emission for Imaging the Restriction and Regulation of Biosynthesis of Cys and GSH

Author: Huming Yan, Fangjun Huo, Yongkang Yue, Jianbin Chao, Caixia Yin

Issue&Volume: December 24, 2020

Abstract: Biosynthesis is a necessary process to maintain life. In recent years, research has fully shown that three kinds of biothiols (Cys, Hcy, GSH) mainly play the role in oxidative stress and maintaining cell homeostasis in cells, and that abnormal concentrations will lead to the occurrence of cardiovascular diseases, cancers, etc. Various fluorescent probes have shown unprecedented advantages in detecting their concentrations and studying their biological functions. As a matter of fact, these three kinds of biothiols are generated in the process of biosynthesis in vivo. It is of great significance to understand their biosynthetic pathways and elucidate their synthetic relationships. In this work, to α,β-unsaturated ketones conjugated ethylenediamine coumarin and pyrandione was introduced boron fluoride and, through its strong electron deficiency effect, afforded a molecule having near-infrared emission and regulated the rigidity of molecules. At the same time, the conjugated double bond is used to respond to molecular rigidity. The rapid response of the probe to biothiols and the slow dissociation aggregation of the probe itself through the response environment could monitor the absence of biothiols in cells. In addition, based on the difference in sensitivity of response of Cys and GSH to the probe, this work studied the interaction between biosynthetic pathways of Cys and GSH in cells through enzyme inhibition for the first time. The relationship of restriction and regulation of biosynthesis in vivo was revealed.

DOI: 10.1021/jacs.0c10840

Source: https://pubs.acs.org/doi/10.1021/jacs.0c10840

期刊信息

JACS:《美国化学会志》,创刊于1879年。隶属于美国化学会,最新IF:14.612
官方网址:https://pubs.acs.org/journal/jacsat
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