Design and synthesis of a new environmentally sensitive small-molecule fluorescent probe for MRGPRX2

IF 4.1 3区工程技术 Q2 CHEMISTRY, APPLIED

Dyes and Pigments Pub Date : 2025-04-05 DOI:10.1016/j.dyepig.2025.112815

Xiaoxue Mo , Yuexin Lv , Jiayu Lu , Yajing Hou , Hua Qian , Cheng Wang , Huaizhen He

{"title":"Design and synthesis of a new environmentally sensitive small-molecule fluorescent probe for MRGPRX2","authors":"Xiaoxue Mo , Yuexin Lv , Jiayu Lu , Yajing Hou , Hua Qian , Cheng Wang , Huaizhen He","doi":"10.1016/j.dyepig.2025.112815","DOIUrl":null,"url":null,"abstract":"<div><div>MAS-related G protein-coupled receptor X2 (MRGPRX2) is a key target receptor and an important drug target for triggering pseudo-allergic reactions. Studying its ligands will help to understand the mechanism of pseudo-allergic reactions and discover anti-allergic drugs. Small-molecule fluorescent probes are widely used to study the localization of G protein-coupled receptors (GPCRs) on the cell membrane, the transport and internalization of GPCRs, and the interaction between receptors and ligands due to their high selectivity, sensitivity and safety. MRGPRX2 is one of GPCRs with an active hydrophobic ligand binding domain, so designing small-molecule fluorescent probes with environmental sensitivity is very important for the study of MRGPRX2 ligands and the visualization of this receptor. In this study, we selected the agonist of MRGPRX2 (<em>R</em>)-ZINC-3573 as the recognition group and used different fluorophore skeleton structures as the luminescent group to synthesize a series of small-molecule fluorescent probes targeting MRGPRX2. Among them, PoX2-B with BODIPY FL as the fluorescent group had good photostability and environmentally sensitive properties to the hydrophobic ligand binding domain of MRGPRX2, and could be used for living cell imaging. Furthermore, PoX2-B could specifically recognize MRGPRX2, and it was expected to be used to screen effective ligands of MRGPRX2 in the future, so as to play a role in the development of anti-allergy drugs and the pathogenesis of allergic diseases.</div></div>","PeriodicalId":302,"journal":{"name":"Dyes and Pigments","volume":"240 ","pages":"Article 112815"},"PeriodicalIF":4.1000,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Dyes and Pigments","FirstCategoryId":"88","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0143720825001858","RegionNum":3,"RegionCategory":"工程技术","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, APPLIED","Score":null,"Total":0}

引用次数: 0

Abstract

MAS-related G protein-coupled receptor X2 (MRGPRX2) is a key target receptor and an important drug target for triggering pseudo-allergic reactions. Studying its ligands will help to understand the mechanism of pseudo-allergic reactions and discover anti-allergic drugs. Small-molecule fluorescent probes are widely used to study the localization of G protein-coupled receptors (GPCRs) on the cell membrane, the transport and internalization of GPCRs, and the interaction between receptors and ligands due to their high selectivity, sensitivity and safety. MRGPRX2 is one of GPCRs with an active hydrophobic ligand binding domain, so designing small-molecule fluorescent probes with environmental sensitivity is very important for the study of MRGPRX2 ligands and the visualization of this receptor. In this study, we selected the agonist of MRGPRX2 (R)-ZINC-3573 as the recognition group and used different fluorophore skeleton structures as the luminescent group to synthesize a series of small-molecule fluorescent probes targeting MRGPRX2. Among them, PoX2-B with BODIPY FL as the fluorescent group had good photostability and environmentally sensitive properties to the hydrophobic ligand binding domain of MRGPRX2, and could be used for living cell imaging. Furthermore, PoX2-B could specifically recognize MRGPRX2, and it was expected to be used to screen effective ligands of MRGPRX2 in the future, so as to play a role in the development of anti-allergy drugs and the pathogenesis of allergic diseases.

Abstract Image

查看原文本刊更多论文

新型环境敏感MRGPRX2小分子荧光探针的设计与合成

mas相关G蛋白偶联受体X2 （MRGPRX2）是引发假性过敏反应的关键靶受体和重要药物靶点。对其配体的研究将有助于了解假性过敏反应的机制和发现抗过敏药物。小分子荧光探针因其高选择性、高灵敏度和高安全性，被广泛用于研究G蛋白偶联受体（gpcr）在细胞膜上的定位、gpcr的转运和内化以及受体与配体的相互作用。MRGPRX2是具有活性疏水配体结合域的gpcr之一，因此设计具有环境敏感性的小分子荧光探针对于MRGPRX2配体的研究和该受体的可视化非常重要。本研究选择MRGPRX2的激动剂(R)-ZINC-3573作为识别基团，采用不同的荧光团骨架结构作为发光基团，合成了一系列靶向MRGPRX2的小分子荧光探针。其中以BODIPY FL为荧光基团的PoX2-B对MRGPRX2的疏水配体结合域具有良好的光稳定性和环境敏感性，可用于活细胞成像。此外，PoX2-B能够特异性识别MRGPRX2，未来有望用于筛选MRGPRX2的有效配体，从而在抗过敏药物的开发和变应性疾病的发病机制中发挥作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Dyes and Pigments 工程技术-材料科学：纺织

CiteScore

8.20

自引率

13.30%

发文量

933

审稿时长

33 days

期刊介绍： Dyes and Pigments covers the scientific and technical aspects of the chemistry and physics of dyes, pigments and their intermediates. Emphasis is placed on the properties of the colouring matters themselves rather than on their applications or the system in which they may be applied. Thus the journal accepts research and review papers on the synthesis of dyes, pigments and intermediates, their physical or chemical properties, e.g. spectroscopic, surface, solution or solid state characteristics, the physical aspects of their preparation, e.g. precipitation, nucleation and growth, crystal formation, liquid crystalline characteristics, their photochemical, ecological or biological properties and the relationship between colour and chemical constitution. However, papers are considered which deal with the more fundamental aspects of colourant application and of the interactions of colourants with substrates or media. The journal will interest a wide variety of workers in a range of disciplines whose work involves dyes, pigments and their intermediates, and provides a platform for investigators with common interests but diverse fields of activity such as cosmetics, reprographics, dye and pigment synthesis, medical research, polymers, etc.