基于异吲哚啉的荧光探针，带有自毁连接基，用于灵敏且选择性地检测O-连接的N-乙酰葡糖胺酶活性。

Isoindoline-based fluorogenic probes bearing a self-immolative linker for the sensitive and selective detection of O-GlcNAcase activity.

作者信息

Wu Yuan-Hao, Wang Guan-Jun, Guo Chen, Wang Pei-Pei, Wang Jun-Yi, Hu Xi-Le, Zang Yi, James Tony D, Li Jia, He Xiao-Peng

机构信息

Key Laboratory for Advanced Materials and Joint International Research Laboratory of Precision Chemistry and Molecular Engineering, Feringa Nobel Prize Scientist Joint Research Center, School of Chemistry and Molecular Engineering, East China University of Science and Technology, 130 Meilong Rd, Shanghai 200237, China.

National Center for Drug Screening, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.

出版信息

Chem Commun (Camb). 2024 Aug 1;60(63):8240-8243. doi: 10.1039/d4cc02845g.

DOI:10.1039/d4cc02845g

PMID:39007923

Abstract

O-GlcNAcase (OGA) is implicated in several important biological and disease-relevant processes. Here, we synthesized fluorogenic probes for OGA by grafting GlcNAc directly or using a self-immolative linker to the hydroxyl position of 4-hydroxylisoindoline (BHID), a typical excited-state intramolecular proton transfer (ESIPT) probe. The probe was used for a fluorogenic assay to determine the half maximal inhibitory concentration of a known OGA inhibitor and differentiate between OGA and hexosaminidase when GlcNAc is replaced by GlcNPr, where a propionyl group is used instead of an acetyl group.

摘要

O-连接的N-乙酰葡糖胺酶（OGA）参与了多个重要的生物学过程以及与疾病相关的过程。在此，我们通过将N-乙酰葡糖胺直接连接或使用自毁型连接子连接到4-羟基异吲哚啉（BHID，一种典型的激发态分子内质子转移（ESIPT）探针）的羟基位置，合成了用于OGA的荧光探针。该探针用于荧光测定，以确定一种已知OGA抑制剂的半数最大抑制浓度，并在将N-乙酰葡糖胺替换为N-丙酰葡糖胺（其中使用丙酰基代替乙酰基）时区分OGA和己糖胺酶。