相关实验视频

Updated: Jul 31, 2025

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Chemical Inactivation of the E3 Ubiquitin Ligase Cereblon by Pomalidomide-based Homo-PROTACs

Published on: May 15, 2019

针对Clp的BacPROTACs会损害菌根蛋白质稳定和生存

David M Hoi¹, Sabryna Junker², Lukas Junk³

¹Research Institute of Molecular Pathology, Vienna BioCenter, 1030 Vienna, Austria; Max Perutz Labs, Vienna BioCenter, 1030 Vienna, Austria; Vienna BioCenter PhD Program, Doctoral School of the University of Vienna and Medical University of Vienna, 1030 Vienna, Austria; University of Vienna, Center for Molecular Biology, Department for Biochemistry and Cell Biology, 1030 Vienna, Austria.

|May 3, 2023

概括

新的抗结核药物BacPROTACs针对Mycobacterium结核病中的Clp蛋白酶系统. 这些药物降解了ClpC1和ClpC2,显示出抗结核的功效增加了100倍以上.

科学领域:

微生物学
分子生物学
药物发现

背景情况:

ClpC1:ClpP1P2蛋白酶对于维护菌根体中的蛋白质稳态 (蛋白质稳态) 是至关重要的.
目前针对Clp蛋白酶的抗结核药物有效性有限.
菌根菌具有可能赋予耐药性的应激反应因子.

研究的目的:

阐明抗结核抗生素cyclomarin A和ecumicin的作用机制.
研究新发现的应激反应因子ClpC2和ClpC3的作用.
开发新的治疗策略来克服细菌耐药性机制.

主要方法:

定量蛋白质组学分析抗生素诱导的蛋白质组范围内的变化.
生物化学测试以描述抗生素机制和蛋白质相互作用.
开发和测试一种新的双功能降解剂 (BacPROTAC).

主要成果:

环素A和环素诱导显著的蛋白质不平衡,并对ClpC2和ClpC3进行上调.
ClpC2和ClpC3作为Clp蛋白酶对抗抗生素压力的保护因素.
一种针对ClpC1和ClpC2的新型BacPROTAC显示出对Mycobacterium结核病的功效提高了100倍以上.

结论:

Clp捕食蛋白 (ClpC2,ClpC3) 是菌根蛋白质稳定网络的重要保护剂.
巴克普罗塔克是一种有前途的新型抗生素,对病原菌具有更强的疗效.
通过蛋白质降解向细菌耐药机制为未来药物开发提供了可行的策略.

关键词:

在BacPROTAC 细胞蛋白酶其他:结核菌抗生素环素A 其他药物蛋白质质量控制小分子降解剂有针对性的蛋白质降解

更多相关视频

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

System for Efficacy and Cytotoxicity Screening of Inhibitors Targeting Intracellular Mycobacterium tuberculosis

Published on: April 5, 2017

Author Spotlight: Scalable Drug Screening Protocol for Efficient Discovery of M. abscessus Treatments

Author Spotlight: Scalable Drug Screening Protocol for Efficient Discovery of M. abscessus Treatments

Published on: October 25, 2024

相关概念视频

Targeted Cancer Therapies

Targeted Cancer Therapies

The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...

Defense Against Bacterial Pathogens

Defense Against Bacterial Pathogens

The human immune system is a complex network of cells, tissues, and organs that work together to defend the body against bacterial infections. It consists of various immune cells, each playing a specific role in the defense mechanism.
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...