通过近距离生物化对寡核酸药物的相互作用组进行概述
Alfred Hanswillemenke1, Daniel Tobias Hofacker1, Michèle Sorgenfrei1
1Interfaculty Institute of Biochemistry, University of Tübingen, Tübingen, Germany.
Nature chemical biology
|January 17, 2024
概括
药物识别 (Drug-ID) 通过近距离生物化 (proximity biotinylation) 来识别活细胞中的药物蛋白相互作用. 这种新的方法在本地条件下,使用最小的细胞材料,揭示细胞药物点.
科学领域:
- 生物化学 生物化学
- 分子生物学分子生物学
- 化学生物学 化学生物学
背景情况:
- 了解药物蛋白相互作用对于药物发现和开发至关重要.
- 目前的方法往往缺乏在本地条件下对活细胞内的相互作用进行分析的能力.
- 确定药物和寡核酸的精确点对于有效性和安全性至关重要.
研究的目的:
- 引入Drug-ID,一种新的近距离生物化技术,用于识别活细胞中的药物蛋白相互作用.
- 在原生细胞条件下,分析小分子和反感性寡核酸 (ASO) 的药物蛋白相互作用组.
- 调查ASO修饰和细胞应激对药物蛋白相互作用的影响.
主要方法:
- 药物识别利用药物与生物联酶的共价结合用于向生物化.
- 该方法在药理学上相关的度下识别活细胞内的与药物结合的蛋白质组.
- 使用重组生物联酶开发了一个in situ变体,消除了对细胞遗传操纵的需求.
主要成果:
- 药物识别成功确定了小分子 (JQ1,SAHA) 和反感性寡核酸 (ASO) 的药物蛋白相互作用.
- 该研究描述了剂量依赖的ASO聚合以及ASO化学和长度对蛋白质相互作用的影响.
- 由actinomycin D诱导的细胞内相互作用变化被使用in situ药物-ID变体检测到.
结论:
- 药物识别为活细胞中药物蛋白相互作用体的新型定型提供了一个强大的工具.
- 该方法提供了对药物作用机制,ASO行为和细胞对药物治疗反应的见解.
- 药物识别的适应性和最小样本要求表明了 in vivo 应用的潜力和在化学生物学中的广泛用途.
相关概念视频
02:26Protein Networks
4.0K
An organism can have thousands of different proteins, and these proteins must cooperate to ensure the health of an organism. Proteins bind to other proteins and form complexes to carry out their functions. Many proteins interact with multiple other proteins creating a complex network of protein interactions.
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
These interactions can be represented through maps depicting protein-protein interaction networks, represented as nodes and edges. Nodes are circles that are representative of a protein,...
4.0K
02:04Protein-protein Interfaces
12.5K
Many proteins form complexes to carry out their functions, making protein-protein interactions (PPIs) essential for an organism's survival. Most PPIs are stabilized by numerous weak noncovalent chemical forces. The physical shape of the interfaces determines the way two proteins interact. Many globular proteins have closely-matching shapes on their surfaces, which form a large number of weak bonds. Additionally, many PPIs occur between two helices or between a surface cleft and a...
12.5K
03:31Labeling DNA Probes
8.2K
DNA probes are fragments of DNA labeled with a reporter tag to enable their detection or purification. The resulting labeled DNA probes can then hybridize to target nucleic acid sequences through complementary base-pairing, and may be used to recover or identify these regions.
Radioisotopes, fluorophores, or small molecule binding partners like biotin or digoxigenin, are the most widely used reporter tags for labeling DNA probes. These labels can be attached to the probe DNA molecule via...
Radioisotopes, fluorophores, or small molecule binding partners like biotin or digoxigenin, are the most widely used reporter tags for labeling DNA probes. These labels can be attached to the probe DNA molecule via...
8.2K
02:24Ribosome Profiling
3.5K
Ribosome profiling or ribo-sequencing is a deep sequencing technique that produces a snapshot of active translation in a cell. It selectively sequences the mRNAs protected by ribosomes to get an insight into a cell’s translation landscape at any given point in time.
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
Applications of ribosome profiling
Ribosome profiling has many applications, including in vivo monitoring of translation inside a particular organ or tissue type and quantifying new protein synthesis levels.
The technique...
3.5K