Department of Medicinal Chemistry, School of Pharmacy, Air Force Medical University, Xi'an, 710032, P. R. China.
Institute of Medical Research, Northwestern Polytechnical University, Xi'an, 710072, P. R. China.
Chem Asian J. 2020 May 4;15(9):1464-1468. doi: 10.1002/asia.202000152. Epub 2020 Mar 30.
GSTP1 has been considered to be a marker for malignancy in many tissues. However, the existing GST fluorescent probes are unfavorable for in vivo imaging because of the limited emission wavelength or insufficient fluorescence enhancement (six-fold). The limited fluorescence enhancement of GST fluorescent probes is mainly ascribed to the high background signals resulting from the spontaneous reaction between GSH and the probes. In this work, a highly specific GST probe with NIR emission has been successfully developed through optimization of the essential unit of the probe to repress the spontaneous reaction. The novel GST probe exhibits over 100-fold fluorescence enhancement upon incubation with GSTP1/GSH and high selectivity over other potential interference. In addition, the probe has been proved to be capable of tracking endogenous GST in A549 cells. Finally, the in vivo imaging results demonstrate that the probe can be used for effective imaging of endogenous GST activity in subcutaneous tumor mouse with high contrast.
GSTP1 已被认为是许多组织中恶性肿瘤的标志物。然而，现有的 GST 荧光探针由于发射波长有限或荧光增强不足（六倍），不利于体内成像。GST 荧光探针荧光增强有限主要归因于 GSH 与探针之间自发反应产生的高背景信号。在这项工作中，通过优化探针的基本单元，成功开发出一种具有近红外发射的高度特异的 GST 探针，以抑制自发反应。新型 GST 探针与 GSTP1/GSH 孵育后表现出超过 100 倍的荧光增强，并且对其他潜在干扰具有高选择性。此外，该探针已被证明能够在 A549 细胞中跟踪内源性 GST。最后，体内成像结果表明，该探针可用于有效成像皮下肿瘤小鼠内源性 GST 活性，具有高对比度。
