相关实验视频

Updated: Jun 28, 2025

From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding

From Molecules to Materials: Engineering New Ionic Liquid Crystals Through Halogen Bonding

Published on: March 24, 2018

基于SuFEx的化学多样化,用于系统地发现CRBN分子合剂

Trever R Carter¹, Natalia Milosevich¹, Lucas Dada²

¹Department of Chemistry, The Scripps Research Institute, United States.

Bioorganic & medicinal chemistry

|April 12, 2024

概括

分子粘合剂稳定蛋白质相互作用以进行有针对性的降解,比PROTACs具有优势. 这项研究开发了一种使用硫-化物交换的新方法,以发现针对GSPT1蛋白的新型Cereblon (CRBN) 分子.

科学领域:

药用化学医学化学
化学生物学化学生物学
药物发现药物发现药物发现

背景情况:

分子是稳定蛋白质与蛋白质相互作用的小分子,可实现向蛋白质降解.
虽然提供优势比蛋白质溶解向仿真体 (PROTACs),分子合剂缺乏合理的设计原则.
基于cereblon (CRBN) 的分子可以被修改以改变新基质的特异性.

研究的目的:

开发一种新的化学多样化战略,用于发现Cereblon (CRBN) 分子.
探索使用并行硫-化物交换 (SuFEx) 转换来修改CRBN配体.
为了识别具有改变新基质特异性的新分子.

主要方法:

使用并行SuFEx反应,对CRBN配体5'-氨基莱纳利多米德进行高通量化学多样化.
合成了超过3000种5'-氨基氨基基利胺胺类同类物.
原产品的表型查,以检测细胞活力,以确定活性化合物.

主要成果:

从合成的库中确定了数十种具有差异化活动的类似物.
四种化合物被描述为有效降解G-to-S相转换1 (GSPT1) 蛋白质的化合物.
证明了基于SuFEx发现CRBN分子的概念验证.

结论:

硫-化物交换 (SuFEx) 是快速化学多样化和发现分子的可行策略.
这种方法可以识别具有特定新基质准能力的新型CRBN分子合剂.
这些发现为开发新的向蛋白质降解疗法提供了基础.

关键词:

编号:CRBN 编号:CRBN 编号:CRBN 编号:CRBN 编号:CRBN 编号:CRBN 编号:CRBN 降解降解是一种降解.GSPT1 一个问题莱纳利多胺是什么?分子粘合剂是一种分子粘合剂.SuFEx SuFEx 是一个

更多相关视频

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

Efficient Synthesis of All-Carbon Quaternary Centers via the Conjugate Addition of Functionalized Monoorganozinc Bromides

Published on: May 26, 2019

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

相关概念视频

Radical Substitution: Allylic Bromination

Radical Substitution: Allylic Bromination

In organic synthesis, the formation of products can be altered by changing the reaction conditions. For example, a dibromo addition product is formed when propene is treated with bromine at room temperature. In contrast, propene undergoes allylic substitution in non-polar solvents at high temperatures to give 3-bromopropene. In order to avoid the addition reaction, the bromine concentration must be kept as low as possible throughout the reaction. This can be achieved using N-bromosuccinimide...

Hybridization of Atomic Orbitals I

Hybridization of Atomic Orbitals I

The mathematical expression known as the wave function, ψ, contains information about each orbital and the wavelike properties of electrons in an isolated atom. When atoms are bound together in a molecule, the wave functions combine to produce new mathematical descriptions that have different shapes. This process of combining the wave functions for atomic orbitals is called hybridization and is mathematically accomplished by the linear combination of atomic orbitals. The new orbitals that...

Supercritical Fluid Chromatography

Supercritical Fluid Chromatography

Supercritical fluid chromatography (SFC) provides a beneficial substitute for gas chromatography (GC) and liquid chromatography (LC) for certain samples because it merges the top attributes of both techniques. SFC allows the separation and analysis of compounds that GC or LC does not easily manage. These compounds are traditionally nonvolatile or thermally unstable, making GC unsuitable and lacking functional groups required for HPLC analysis.
SFC utilizes a supercritical fluid mobile phase,...