相关实验视频

Updated: Jul 16, 2025

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

基于碎片和结构引导的穿孔素抑制剂的发现

Jiney Jose¹, Ruby H P Law², Eleanor W W Leung³

¹Auckland Cancer Society Research Centre, Faculty of Medical and Health Sciences, The University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand; Maurice Wilkins Centre for Molecular Biodiscovery, A New Zealand Centre for Research Excellence, Auckland, New Zealand.

European journal of medicinal chemistry

|September 16, 2023

概括

研究人员将达普森确定为孔素连接体,并开发出强大的纳米分子抑制剂. 这些新型分子的目标是穿孔素.

科学领域:

免疫学免疫学免疫学
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:

珀福林是细胞毒性T和NK细胞功能的关键孔形成蛋白质.
失调的穿孔素活性有助于自身免疫性疾病和移植体排斥.
珀福林是各种疾病治疗干预的关键目标.

研究的目的:

通过基于片段的查来识别新的穿孔素配体.
为了开发强效和选择性抑制器的穿孔素的细胞分解活性.
探索结构导向设计,以改善穿素向治疗方法.

主要方法:

使用NMR和表面等离子体共振 (SPR) 的碎片库选.
对已识别的化合物进行结构导向的修改.
在体外分析包括红细胞溶解和NK细胞介导的细胞毒性.
用连体检测的19FNMR进行结合分析.

主要成果:

确定了4,4-diaminodiphenyl sulfone (dapsone) 作为一个穿孔素连接体.
开发出具有对NK细胞细胞毒性纳米分子抑制活性的达普衍生物.
在免疫突触功能的背景下表现出强大的抑制,而不仅仅是红细胞溶解.
与之前的孔连体相比,获得了优越的物理化学特性和溶解性.

结论:

基于碎片的,结构引导的药物发现是有效的识别穿孔素连接体.
新的纳米分子抑制剂的穿孔素的细胞分解功能已成功开发.
这些抑制剂显示出针对免疫媒介过程的治疗应用的前景.

关键词:

4,4-二氨基二硫 4,4-二氨基二硫基于碎片的药物发现.自然杀手细胞是自然杀手细胞.在Perforin中使用Perforin.在X射线晶体学.

更多相关视频

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

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

相关概念视频

Drug Discovery: Overview

Drug Discovery: Overview

Drug discovery is a multifaceted process involving extensive screening, testing, and optimization of lead compounds to identify potential new drugs for therapeutic use. It combines several approaches, including screening large numbers of natural products, chemical modification of known active molecules, identification of new drug targets, and rational design based on biological mechanisms and drug-receptor structure. These approaches are carried out in both academic research laboratories and...