pH敏感荧光探针Setetrine的分子设计、结构解析与细胞器pH检测
结题报告
批准号:
32000855
项目类别:
青年科学基金项目
资助金额:
24.0 万元
负责人:
李淑昂
依托单位:
学科分类:
结构生物学
结题年份:
2023
批准年份:
2020
项目状态:
已结题
项目参与者:
李淑昂
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中文摘要
细胞内细胞器pH的精确测量对于细胞代谢认知、代谢干预及疾病治疗具有重要意义。pH敏感荧光蛋白是利用荧光蛋白法测量细胞器pH的重要工具。为实现多种细胞器pH的同时测量并提高pH测量精确度,我们前期通过结构设计研发了具有宽pH响应范围(pH3.5-9.0)、高荧光量子产率、“单激发双发射”特性而可用比率法精准测量细胞器pH的新型pH敏感蛋白Setetrine。为了探究其对pH敏感的分子机制和在细胞生物学的实际应用价值,本项目拟解析该新型荧光蛋白在不同pH时的晶体结构,并以其为探针建立细胞内完整的细胞器pH图谱,研究细胞器pH改变与肿瘤细胞代谢的相关性。进一步利用小分子干预探究靶向各细胞器作为抗肿瘤治疗策略的可行性。预期为肿瘤细胞代谢研究和靶向各细胞器的抗肿瘤药物设计提供理论和实验依据。
英文摘要
Accurate measurement of intracellular organelles pH is of great significance for the recognition of cell metabolism, metabolic intervention and disease treatment. pH sensitive fluorescent protein is an important tool for measuring the organelles pH. In order to achieve pH measurement of various organelles and improve pH measurement accuracy, we developed a new pH sensitive probe Setetrine with wide pH response range (pH3.5-9.0), high fluorescence quantum yield, and single excitation and double emission characteristics, which can be used to accurately measure the organelles pH by ratio method. In order to explore the molecular mechanism of its sensitive to pH and in the actual application value of cell biology, the project is proposed to resolve the new fluorescent protein crystal structure in different pH, to use this probe to set up intact organelles pH graph, to study the relationship between the organelles pH change and tumor cell metabolism, to use the small molecule intervention to explore the feasibility of anti-tumor therapy strategies targeting various organelles. It is expected to provide theoretical and experimental basis for the study of tumor cell metabolism and designing anti-tumor drugs for targeting various organelles.
期刊论文列表
专著列表
科研奖励列表
会议论文列表
专利列表
Progress in pH-Sensitive sensors: essential tools for organelle pH detection, spotlighting mitochondrion and diverse applications.
pH敏感传感器的进展:细胞器pH检测的基本工具,焦点线粒体和不同的应用。
DOI:10.3389/fphar.2023.1339518
发表时间:2023
期刊:Frontiers in pharmacology
影响因子:5.6
作者:
通讯作者:
DOI:10.3389/fphys.2022.977431
发表时间:2022
期刊:FRONTIERS IN PHYSIOLOGY
影响因子:4
作者:Meng, Xiao-Yan;Wang, Dian-Dian;Xie, Tao-Rong;Yang, Run-Zhou;Liu, Chun-Feng;Liu, Dan-Hua;Li, Shu-Ang;Luan, Yi;Kang, Jian-Sheng
通讯作者:Kang, Jian-Sheng
DOI:10.1016/j.scr.2024.103328
发表时间:2024
期刊:Stem Cell Research
影响因子:1.2
作者:Shu-Ang Li;Ying-Jie Zhang;Yong-Qing Zhu;Xiao-Yan Meng;Cai-Li Chen;Pei-Pei Liu;Wei Sun
通讯作者:Wei Sun
国内基金
海外基金