相关实验视频

Updated: Sep 1, 2025

Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases

Using Phage Display to Develop Ubiquitin Variant Modulators for E3 Ligases

Published on: August 27, 2021

通过菌体显示发现素向的可逆共价配体

Mengmeng Zheng¹, Fa-Jie Chen¹, Kaicheng Li¹

¹Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, Massachusetts 02467, United States.

Journal of the American Chemical Society

|August 17, 2022

概括

用菌体显示来制造新的可逆共价抑制剂. 这种新方法成功地确定了细菌和病毒蛋白的强联体,为药物发现提供了多功能平台.

科学领域:

医学化学
生物技术
药物发现

背景情况:

可逆共价键形成是设计强效蛋白抑制剂的一种有效策略,比如博尔特佐米布和沃克塞洛托.
这种抑制剂的合理设计是具有挑战性的,即使是现有的非对应性支架.

研究的目的:

开发一种用于产生可逆共价抑制剂的菌体显示平台.
将2-乙乙酸 (APBA) 作为可逆共价结合于氨酸残留物的弹头.

主要方法:

构建具有APBA的化学修饰菌体库 (线性和循环).
对呈现APBA的菌体库进行查,以对抗Sortase A (金黄色葡萄球菌) 和SARS-CoV-2尖端蛋白.
结构与活动关系研究以证实APBA弹头的作用.

主要成果:

对两种蛋白具有单位微分子功率和高特异性的联体的鉴定.
使用已识别的配体,证明活细胞类酶抑制和敏感尖端蛋白检测.
结构活性研究的明确证据强调APBA弹头对蛋白质结合的益处.

结论:

这项研究确立了菌体显示为开发可逆共价抑制剂对治疗标的可行方法.
呈现APBA的菌体显示平台广泛适用于发现各种蛋白质的抑制剂,包括那些参与蛋白质与蛋白质相互作用的抑制剂.

更多相关视频

A Protocol for Phage Display and Affinity Selection Using Recombinant Protein Baits

A Protocol for Phage Display and Affinity Selection Using Recombinant Protein Baits

Published on: February 16, 2014

Bacterial Peptide Display for the Selection of Novel Biotinylating Enzymes

Bacterial Peptide Display for the Selection of Novel Biotinylating Enzymes

Published on: October 3, 2019

相关概念视频

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...