Li Xiangmin, Zheng Yongjun, Tong Hongjuan, Qian Rui, Zhou Lin, Liu Guixia, Tang Yun, Li Hao, Lou Kaiyan, Wang Wei
Shanghai Key Laboratory of New Drug Design, Shanghai Key Laboratory of Chemical Biology, School of Pharmacy and State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, 130 Meilong Road, Shanghai, 200237, P. R. China.
Department of Chemistry & Chemical Biology, University of New Mexico, MSC03 2060, Albuquerque, NM, 87131-0001, USA.
Chemistry. 2016 Jun 27;22(27):9247-56. doi: 10.1002/chem.201601126. Epub 2016 May 31.
Differentiation of biologically important thiols, such as cysteine (Cys), homocysteine (Hcy), and glutathione (GSH) is still a challenging task. Herein, we present a novel fluorescent chemodosimeter capable of selectively detecting Cys over other biothiols including Hcy and GSH and other amino acids by a facile thiol-Michael addition/transcyclization rearrangement cascade click process. The unique transcyclization step is critical for the selectivity as a result of the kinetically favorable formation of a six-membered ring with the Cys Michael adduct. Moreover, the probe adopts a distinctive dual quenching mechanism-photoinduced electron transfer (PET) and photoinduced intramolecular charge transfer (ICT) to deliver a drastic turn-on fluorescence response only at the Cys-selective transcylization step. The judicious selection of strong electron-withdrawing naphthalimide fluorophore with maleimide group enhances the electrophilicity and thus reactivity for the cascade process leading to fast detection and ultrasensitivity with a detection limit of 2.0 nm (S/N=3). The probe has demonstrated its practical utility potential in Cys imaging in live cells.
区分具有生物学重要性的硫醇，如半胱氨酸（Cys）、同型半胱氨酸（Hcy）和谷胱甘肽（GSH），仍然是一项具有挑战性的任务。在此，我们展示了一种新型荧光化学传感器，它能够通过简便的硫醇-迈克尔加成/反环化重排级联点击过程，选择性地检测Cys，而不包括Hcy、GSH等其他生物硫醇以及其他氨基酸。独特的反环化步骤对于选择性至关重要，这是由于与Cys迈克尔加合物形成六元环在动力学上有利。此外，该探针采用独特的双重猝灭机制——光诱导电子转移（PET）和光诱导分子内电荷转移（ICT），仅在Cys选择性反环化步骤产生强烈的荧光开启响应。带有马来酰亚胺基团的强吸电子萘二甲酰亚胺荧光团的明智选择增强了亲电性，从而提高了级联过程的反应活性，实现了快速检测和超灵敏性，检测限为2.0 nM（S/N=3）。该探针已在活细胞中Cys成像方面展示了其实际应用潜力。
