生物催化剂由甲[7]uril分子容器调节
1Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA.
Journal of the American Chemical Society
|March 10, 2010
概括
我们开发了新的双面抑制剂,通过与酶和库库比图里尔 (CB) 结合来控制酶活性. 这允许可逆的牛炭酸酶 (BCA) 活动的开关,与稳定抑制乙胆酶 (AChE) 不同.
科学领域:
- 超分子化学 超分子化学
- 酶抑制可以抑制酶.
- 化学生物学 化学生物学
背景情况:
- 酶活性调节对于生物过程和治疗干预至关重要.
- 黄瓜 (CBs) 是宏循环宿主,能够与各种客人形成稳定的包容复合体.
- 开发可控制的酶抑制剂仍然是化学生物学中的一个重大挑战.
研究的目的:
- 合成和描述新型"双面"抑制剂,其具有酶结合和库库比图里尔结合域.
- 研究使用这些抑制剂和CB的可控抑制牛炭酶 (BCA) 和乙胆酶 (AChE) [7].
- 通过超分子复合体形成阐明可逆和不可逆酶抑制的机制.
主要方法:
- 用酶抑制剂和库库比图里尔识别位点合成双功能分子.
- 酶活性测定 (UV/Vis) 用于监测BCA和ACHE的催化速率.
- 光位移测定,1H NMR光谱学和动力测量 (Ka,kon,koff) 用于描述复杂的形成和解离.
主要成果:
- 成功合成了针对BCA和ACHE的双面抑制剂1-5 .
- 通过短暂的BCA-CB[7]三元复合体形成和解离,证明了BCA活动的可逆开关.
- 通过形成热力学稳定的 AChE-CB [7] 三元复合体,实现了稳定,不可逆转的 AChE 抑制.
结论:
- 这种"双面"的抑制剂策略使得可以对酶催化活性进行调节的控制.
- 用BCA实现了可逆抑制,而用AChE观察到不可逆的抑制,这取决于复杂的稳定性.
- 这种方法提供了一个不同的机制,以控制酶活性,与自然的全调节相比.
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