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科学家开发出一种生物正交的、可视的、靶向线粒体的硫化氢输送系统
作者:小柯机器人 发布时间:2021/11/24 16:16:36

南京大学化学化工学院Yong Liang团队开发出一种生物正交的、可视的、靶向线粒体的硫化氢(H2S)输送系统。相关论文于2021年11月22日在线发表在《德国应用化学》杂志上。

在密度泛函理论(DFT)计算的帮助下,研究人员设计了一种新的1,3-二硫醇-4-酸酯(DTO)化合物,它可以通过1,3-二极环加成和逆-Diels-Alder反应与炔发生反应,生成作为H2S前体的羰基硫化物(COS),以及具有开启荧光的噻吩衍生物。此外,DTO中的二苯基氨基取代基大大增加了这种H2S传递系统的线粒体靶向性。这种生物正交的点击释放反应首次在一个系统中整合了三种功能:(1)原位可控的H2S释放,(2)伴随的荧光反应,以及(3)线粒体靶向传递。

此外,研究人员还揭示了在H9c2细胞中使用该系统在氧化压力下减轻线粒体膜电位损失的问题。

据介绍,H2S是一种重要的内源性气体传导物质,但外源性H2S的定向输送和实时反馈仍具有挑战性。

附:英文原文

Title: Design and Development of a Bioorthogonal, Visualizable and Mitochondria-Targeted Hydrogen Sulfide (H2S) Delivery System

Author: Yinghan Chen, Ruohan Zhao, Cheng Tang, Chun Zhang, Wenyuan Xu, Luyan Wu, Yuqi Wang, Deju Ye, Yong Liang

Issue&Volume: 2021-11-22

Abstract: Hydrogen sulfide (H2S) is an important endogenous gasotransmitter, but the targeted delivery and real-time feedback of exogenous H2S are still challenging. With the aid of density functional theory (DFT) calculations, we designed a new 1,3-dithiolium-4-olate (DTO) compound, which can react with a strained alkyne via the 1,3-dipolar cycloaddition and the retro-Diels-Alder reaction to generate carbonyl sulfide (COS) as the precursor of H2S, and a thiophene derivative with turn-on fluorescence. Moreover, the diphenylamino substituent in DTO greatly increases the mitochondrial targeting of this H2S delivery system. Such a bioorthogonal click-and-release reaction has integrated three functions in one system for the first time: (1) in-situ controllable H2S release, (2) concomitant fluorescence response, and (3) mitochondria-targeted delivery. In addition, we investigated the mitochondrial membrane potential loss alleviation by using this system in H9c2 cells under oxidative stress.

DOI: 10.1002/anie.202112734

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202112734

期刊信息

Angewandte Chemie:《德国应用化学》,创刊于1887年。隶属于德国化学会,最新IF:12.959
官方网址:https://onlinelibrary.wiley.com/journal/15213773
投稿链接:https://www.editorialmanager.com/anie/default.aspx