寻找针对IA型拓酶的特定抑制剂
Somaia Haque Chadni1, Shomita Ferdous1, Yuk-Ching Tse-Dinh2
1Biochemistry PhD Program, Florida International University, Miami, FL, USA; Biomolecular Sciences Institute, Florida International University, Miami, FL, USA.
类型IA拓酶在细菌和真核生物中至关重要,具有潜在的药物标. 目前的抑制剂缺乏强度和选择性,阻碍了抗菌和抗癌疗法的开发.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 药物发现 药物发现 药物发现
背景情况:
- 类型IA型拓酶,包括细菌拓酶I和III,以及真核生物拓酶III,是必不可少的酶.
- 这些酶在DNA拓中起着关键作用,对神经发育 (人类TOP3B),癌症和传染病有影响.
研究的目的:
- 以突出类型IA的拓聚酶作为治疗干预的新目标.
- 审查目前开发这些酶的小分子抑制剂的策略和挑战.
主要方法:
- 计算方法,如对接和机器学习.
- 高通量查 (HTS) 包括基于酶和基于细胞的测定.
- 对IA型拓酶抑制剂的现有文献进行分析.
主要成果:
- 确定了IA型拓聚酶作为抗菌,抗癌,抗病毒和抗寄生虫剂的潜在标.
- 选活动已经产生了抑制催化活性或捕获共价复合体的化合物.
- 现有的细菌拓酶I和人类TOP3B的小分子抑制剂显示出不足的效力和选择性.
结论:
- 类型IA拓酶代表了新疗法的有希望的标.
- 克服缺乏结构数据和目标验证等挑战对于开发有效的抑制剂至关重要.
- 对于未来的药物发现工作,建议采用集成的虚拟和实验查方法.
更多相关视频
10:12Author Spotlight: Quantitative Detection of DNA Protein Crosslinks and Their Post-Translational Modifications
Published on: April 21, 2023
06:07Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
Published on: August 5, 2022
相关概念视频
DNA Topoisomerases
Types and Mechanism of action
Topoisomerases are divided into two main types. ...
Eukaryotic Transcription Inhibitors
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
Enzyme Inhibition
Indirect-Acting Cholinergic Agonists: Chemistry and Structure-Activity Relationship
Reversible inhibitors display short to medium durations of action. Short-acting agents include simple alcohols with...
Indirect-Acting Cholinergic Agonists: Mechanism of Action
Reversible inhibitors like edrophonium bind to a specific part of the enzyme called the anionic catalytic site. They form noncovalent bonds, which means they are not strongly attached to the enzyme. This creates a temporary and less stable enzyme–inhibitor complex,...
The Electron Transport Chain
Inhibitors of the electron transport chain
Rotenone, a widely used pesticide, prevents electron transfer from Fe-S cluster to ubiquinone or Q...
