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Ligand Binding Sites

Ligand Binding Sites

Proteins are dynamic macromolecules that carry out a wide variety of essential processes; however, the activities of most proteins depend on their interactions with other molecules or ions, known as ligands.
Protein-ligand interactions are quite specific; even though numerous potential ligands surround a cellular protein at any given time, only a particular ligand can bind to that protein. Moreover, a ligand binds only to a dedicated area on the surface of the protein, known as the...

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Updated: Jun 19, 2026

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

一个基于碎片的竞争F LB-NMR平台用于热点导向的干剖析.

William J McCarthy^1,2, Sherine E Thomas^3,4, Tayo Olaleye¹

¹Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge, UK, CB2 1EW.

Angewandte Chemie (International ed. in English)

|June 19, 2024

概括

我们开发了一个新的查平台,使用具有竞争力的19F基核磁共振 (LB-NMR) 来精确量化蛋白热点的基结合. 这种方法通过在高分辨率下绘制配体相互作用,使有效的热点导向药物发现成为可能.

关键词:

药物发现药物发现药物发现酶是一种酶.化物化物化物基于碎片的发现发现.核磁共振光谱法 (NMR) 是一种光谱法.

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NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode

Published on: June 4, 2021

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Published on: May 16, 2021

相关实验视频

Last Updated: Jun 19, 2026

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Biosensor-based High Throughput Biopanning and Bioinformatics Analysis Strategy for the Global Validation of Drug-protein Interactions

Published on: December 1, 2020

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode

Published on: June 4, 2021

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Nano-Differential Scanning Fluorimetry for Screening in Fragment-based Lead Discovery

Published on: May 16, 2021

科学领域:

生物化学生化学
结构生物学结构生物学
化学生物学化学生物学

背景情况:

带结合热点对于有效的药物设计至关重要.
目前的方法往往缺乏用于热点指导的连接体分析的定量分析.
准热点可以最大限度地提高连接体结合效率.

研究的目的:

引入基于碎片的竞争性19F基基核磁共振 (LB-NMR) 查平台.
为了实现常规化,定量性连接体分析专注于连接体结合热点.
为了证明平台对热点导向的连接体发现的实用性.

主要方法:

对960种化合物进行基于碎片的查,以对抗Mycobacterium abscessus PPAT.
用X射线晶体学来识别联结热点.
为每个热点设计和合成19F记者分子.
竞争性19F LB-NMR测定用于连接体结合概况.

主要成果:

在Mabs PPAT活性部位上确定了三个不同的联结热点.
为每个已识别的热点开发了特定的19F记者.
竞争性19F LB-NMR准确地回顾了绑定亲和关系和地点分配.
结果与ITC和X射线晶体学等传统方法相对相关.

结论:

基于碎片的竞争性19F LB-NMR平台提供了对联体形的定量,热点级别的分辨率.
这个平台对于有效的药物发现有价值,因为它专注于关键的相互作用点.
该方法建立了一个强大的方法来优化在已识别的热点上的联结结合.