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Updated: Dec 23, 2025

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Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
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作为可调节的,对半氨酸反应的电的2-硫烯
Claudio Zambaldo1, Ekaterina V Vinogradova1, Xiaotian Qi2
1Department of Chemistry, The Scripps Research Institute, La Jolla, California 92037, United States.
Journal of the American Chemical Society
|April 18, 2020
概括
研究人员使用KEAP1-NRF2途径发现了新的囊反应化学探针. 这导致了选择性向蛋白质的2-硫胺化合物,包括腺脱氨酶 (ADA),为新的共价药物提供了潜力.
科学领域:
- 化学生物学
- 医学化学
- 蛋白质组学
背景情况:
- 作为化学探针和治疗剂,共价联体越来越重要.
- 为了实现多样化的蛋白质组向,需要扩大囊反应电友的范围.
- 在哺乳动物细胞中,KEAP1-NRF2通路作为内生传感器.
研究的目的:
- 通过基于记者的屏幕发现新型的氨酸反应性电友片段.
- 开发一个模块化和可调节的平台来准反应性氨酸.
- 为了说明新发现的电友系列的药理潜力.
主要方法:
- 使用KEAP1-NRF2通路记者测定来选NRF2激活剂.
- 鉴定和表征2 - 硫胺衍生物作为囊反应电友.
- 在选择性醇反应中采用核芳香替代 (SNAr).
- 设计和合成了一种选择性共价修饰剂的腺脱氨酶 (ADA).
主要成果:
- 发现了一系列通过SNAr选择性与生物醇反应的2-烯.
- 已证明可以调节的电友性和识别元素为2-烯基基架.
- 开发了一种向远端半氨酸的共价ADA抑制剂,减弱了酶活性.
- 通过向ADA的共价修饰剂显示了淋巴细胞增殖的抑制.
结论:
- 引入了一种基于SNAr的多功能反应组,用于向反应性氨酸.
- 验证了2-硫胺系列作为共价药物发现的有前途平台.
- 突出了这些电在调节蛋白质功能和细胞过程中的药理效用.
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