化学蛋白质合成使用第二代N-氨酸尿素连接剂制备-前体的前体
Juan B Blanco-Canosa, Brunello Nardone1, Fernando Albericio2
1‡Departments of Chemistry and Biology, University of Salerno, Via Giovanni Paolo II 132, Fisciano 84084, Italy.
Journal of the American Chemical Society
|May 16, 2015
概括
一种新的N-乙尿素连接剂 (MeDbz) 增强了原生化学结合 (NCL) 的合成. 这种强大的方法可以有效地产生C端-thioesters,从而使复杂的蛋白质组合成为可能,包括富含氨酸的环氧化物.
科学领域:
- 化学生物学 化学生物学
- 有机化学 有机化学
- 蛋白质化学 蛋白质化学
背景情况:
- 原生化学结合 (NCL) 对于蛋白质合成至关重要.
- 对于NCL来说,有效合成C端-thioester是NCL的关键.
- 现有的N-乙尿素 (Nbz) 方法在富含甘氨酸的序列方面存在局限性.
研究的目的:
- 开发一种更强大的方法来合成用于NCL的-thioester.
- 克服以前的N-乙尿素方法的局限性,特别是在富含甘氨酸的上.
- 为了证明新的链接器在合成各种和蛋白质方面具有广泛的适用性.
主要方法:
- 引入了一种新型的N-乙urea连接剂与o-amino(methyl) aniline (MeDbz) 部分.
- 在各种条件下使用MeDbz链接器合成前体,包括微波加热.
- 结合反应的动态分析和适用于富含氨酸的蛋白质合成.
主要成果:
- 该MeDbz链接器使得可靠的链组装,产生所需的N--N'-甲基尿素 (MeNbz) 产品.
- 该方法成功合成了含有所有20种天然氨基酸的.
- MeNbz酸很快转化为酸,促进高效的NCL.
- 成功合成和循环/折叠富含氨酸的蛋白质 (Kalata B1,MCoTI-II) 已经实现.
结论:
- MeDbz链接器提供了一种优越的方法,用于合成NCL的-thioesters.
- 这种方法克服了以前的局限性,并扩大了NCL应用的范围.
- MeDbz链接器有效组装复杂的和富含氨酸的蛋白质.
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