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Constructing Cyclic Peptides Using an On-Tether Sulfonium Center
Published on: September 28, 2022
使用基因修改和蛋白质的N端α-氨基基组
Anna On-Yee Chan1, Chi-Ming Ho, Hiu-Chi Chong
1Department of Chemistry, State Key Laboratory of Synthetic Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
Journal of the American Chemical Society
|February 1, 2012
概括
一种基于基的新方法实现了高度选择性的N端蛋白和的修饰. 这种方法与传统的N-hydroxysuccinimide相比,提供了更高的选择性,从而实现了高效的下游功能化.
科学领域:
- 生物化学 生物化学
- 有机化学 有机化学
- 化学生物学 化学生物学
背景情况:
- 选择性修改蛋白质和对于生物化学研究和治疗开发至关重要.
- 现有的方法往往缺乏N端选择性,导致复杂的产品混合和效率降低.
- 通常使用N-hydroxysuccinimide (NHS) ,但可能导致内部氨基基组的修饰.
研究的目的:
- 开发一种高度选择性的方法,用于和蛋白质的N端修饰.
- 为了比较基基改的选择性与NHS以基改的选择性.
- 为了证明N-终端修饰蛋白对于随后的点击化学功能化的实用性.
主要方法:
- 开发一种与基因组功能化的隔离基因试剂.
- 修改一个库 (XSKFR) 用不同的N端氨基酸,使用基试剂和NHS.
- 使用两种试剂修改各种蛋白质 (胰岛素,溶酶,RNaseA,BCArg).
- 基改性蛋白质通过点击化学的后修改功能化.
主要成果:
- 基试剂对20种酸中13种具有优异的N端选择性 (>99:1) 对其他6种酸具有中度至高的选择性 (4:1至48:1).
- 对于大多数,NHS修饰导致了显著的内部氨酸修饰和较低的N端选择性 (5:1至1:4).
- 使用基因试剂实现了蛋白质的选择性N终端修饰,避免了NHS的多位点修饰.
- 在没有先前治疗的情况下,通过点击化学成功地使用dansyl azide功能化了基改性蛋白质.
结论:
- 隔离的基因为和蛋白质的N端修饰提供了一种高度选择性的方法.
- 这种基于基的方法在选择性和效率方面比NHS化学具有显著的优势.
- 经过N端修改的蛋白质很容易通过点击化学进行进一步的功能化,从而扩大其在生物结合和药物开发中的实用性.
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