原生质谱学促进了DNA编码图书馆技术中的击中验证
Philipp Bittner1, Andreas Gloger2, Michelle Keller2
1Laboratory of Organic Chemistry, Department of Chemistry and Applied Biosciences, ETH Zurich, Zurich, 8093, Switzerland.
Angewandte Chemie (International ed. in English)
|June 3, 2025
概括
用DNA编码的图书馆 (DEL) 技术加速了药物发现. 原生质谱现在通过分析无标记的蛋白质 - 配体相互作用来快速验证DEL的命中,从而加速药物化学.
科学领域:
- 生物化学 生物化学
- 药物发现 药物发现 药物发现
- 分析化学 分析化学
背景情况:
- DNA编码图书馆 (DEL) 技术是药物开发中的一个强大的工具,可以选数十亿种化合物.
- 从DEL选择中验证和描述匹配结果是由于耗时的流程而造成的重大瓶.
研究的目的:
- 引入原生质谱法作为一种方法,用于快速验证来自DEL屏幕的On-DNA化合物.
- 简化DEL技术中的命中识别和表征过程.
主要方法:
- 利用原生质谱法在气相中分析蛋白质和On-DNA配体的非共价复合体.
- 分析纯化的On-DNA结合剂和未纯化的混合物,以评估结合和排名亲缘关系.
主要成果:
- 成功地证明了对纯化On-DNA结合剂的 afinities 的排名能力.
- 展示了从未净化混合物中检测On-DNA化合物的结合的能力,减少了净化需求.
- 提供了对不同分子部分的结合贡献的见解.
结论:
- 原生质谱学为DEL技术中的命中验证提供了一种快速有效的方法.
- 这种方法通过简化成功表征和提供早期洞察结构-活性关系来加速药物化学的努力.
更多相关视频
07:34Large Scale Non-targeted Metabolomic Profiling of Serum by Ultra Performance Liquid Chromatography-Mass Spectrometry UPLC-MS
Published on: March 14, 2013
12.9K
13:26Automated Gel Size Selection to Improve the Quality of Next-generation Sequencing Libraries Prepared from Environmental Water Samples
Published on: April 17, 2015
10.6K
相关概念视频
Mass Spectrometry: Complex Analysis
909
Mass spectrometry is an important technique for the identification of pure compounds. However, it has some limitations for the analysis of complex mixtures, often due to excessive fragmentation making the spectrum too complicated to decipher. Mass spectrometry can be combined with suitable separation methods in sequence, forming hyphenated methods, which are useful in the analysis of complex mixtures.
GC–MS is a powerful hyphenated method commonly used in forensics and environmental...
GC–MS is a powerful hyphenated method commonly used in forensics and environmental...
909
MALDI-TOF Mass Spectrometry
5.3K
Mass spectrometry is a powerful characterization technique that can identify and separate a wide variety of compounds ranging from chemical to biological entities, based on their mass-to-charge ratio (m/z). The instruments that allow this detection, known as mass spectrometers, have three components: an ion source, a mass analyzer, and a detector. These spectrometers differ based on the nature of their ion source and analyzers.
Matrix-assisted laser desorption ionization (MALDI) is a commonly...
Matrix-assisted laser desorption ionization (MALDI) is a commonly...
5.3K
Peptide Identification Using Tandem Mass Spectrometry
6.8K
Tandem mass spectrometry, also known as MS/MS or MS2, is an analytical technique that employs two mass analyzers. Essentially it is a series of mass spectrometers that helps isolate a particular biomolecule and then helps study its chemical properties.
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
This technique helps gather information regarding the protein from which the peptide was obtained and to study the peptides’ amino acid sequence. Identifying peptides from a complex mixture is an important component of the growing field of...
6.8K
Mass Spectrometry: Overview
6.1K
Mass spectrometry is an analytical technique used to determine the molecular mass and molecular formula of a compound. The basic principle of mass spectrometry is to generate ions from the analyte molecule and measure these ion abundances against their molecular mass. One common type of ionization, known as electrospray ionization or EI, bombards the analyte molecules in the gas phase with high-energy electron beams. The electron beams displace an electron from the molecule and leave...
6.1K
