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素加快了蛋白质之间的硫化物交换和化物交换反应

Li Cao¹, Bingchen Yu¹, Paul C Klauser¹

¹Department of Pharmaceutical Chemistry, the, Cardiovascular Research Institute, Helen Diller Family Comprehensive Cancer Center, University of California San Francisco, 94158, San Francisco, California, United States.

Angewandte Chemie (International ed. in English)

|August 8, 2024

概括

在非自然氨基酸附近引入阿尔金因显著加快了硫/的化物交换在蛋白质中的化学作用. 这一突破使新的生物疗法成为可能,并增强了基于细胞的疗法.

科学领域:

生物化学生物化学
化学生物学化学生物学
分子生物学分子生物学

背景情况:

硫化物交换 (SuFEx) 和化物交换 (PFEx) 是点击化学,可以在生物系统中实现精确的共价链接.
通过非自然氨基酸 (UAAS) 将这些化学物质集成到蛋白质中是有希望的,但受到次优反应速率的限制.
现有的催化方法往往与生物环境不相容.

研究的目的:

为了提高蛋白质内的SuFEx和PFEx化学反应速率.
开发一种生物相容的策略,以在生物环境中加速这些点击反应.
设计改进的生物治疗药物,包括细胞参与剂.

主要方法:

将潜在的生物反应性非自然氨基酸 (UAAS) 遗传地纳入蛋白质中.
将氨酸残留物引入与Uaa相邻以调节反应动力学.
测试各种UAS,蛋白质标和条件的反应速率,包括酸性环境.
开发和评估一种新型的共价细胞吸引器.

主要成果:

邻近的阿基尼因显著提高了蛋白质中的SuFEx和PFEx反应速率.
这种增强在各种UAAs,残留物和蛋白质环境中观察到.
在酸性条件下实现了高效的SuFEx反应,克服了以前的限制.
开发出了第一个共价细胞参与者,证明了增强的自然杀手细胞激活.

结论:

靠近氨酸是一种有效的策略,可以加速基于蛋白质的SuFEx和PFEx点击化学.
这种方法提供了一种生物相容的方法,用于在生物研究和药物开发中利用点击化学.
这些发现为先进的生物疗法和改进的细胞疗法铺平了道路.

关键词:

点击"化学"就可以了.协和蛋白质药物协和蛋白质药物遗传密码扩展遗传密码扩展现在的PFEx是什么?SuFEx SuFEx 是一个

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