含有脱水氨酸的的核糖体合成
Florian P Seebeck1, Jack W Szostak
1Howard Hughes Medical Institute and Center for Computational and Integrative Biology, Massachusetts General Hospital, 185 Cambridge Street, Boston, Massachusetts 02114, USA.
Journal of the American Chemical Society
|June 1, 2006
概括
研究人员开发了一种方法,用于合成含有脱氨酸的基因的核糖体合成,使用selenalysine作为掩盖的前体. 这使得能够创建多功能,蛋白质反应性,用于药物发现和分析工具.
科学领域:
- 生物化学 生物化学
- 合成生物学 合成生物学
- 药用化学 医学化学
背景情况:
- 脱氨酸 (Dha) 是一种非蛋白质原性氨基酸,存在于具有治疗功能的天然产品中.
- 达的α,β不和结构提供了刚性和电友性,对改和结合有用.
- 现有的DHA整合方法有限,这阻碍了它在大型组合图书馆中的使用.
研究的目的:
- 开发一种强大的方法,用于含有脱氨酸的的核糖体合成.
- 为了能够创建基因编码的,结合性类图书馆,其中包括DHA.
- 促进用于治疗和分析应用的新型蛋白反应化合物的制备.
主要方法:
- 招募 selenalysine,一个含有的 lysine 模拟物,作为一个掩盖的 Dha 等价物.
- 使用复制的大肠杆菌翻译系统将单氨酸纳入中.
- 在温和的氧化条件下,西莱纳的翻译后转化为Dha.
主要成果:
- 效率高和高忠实度的 ribozomal 纳入 selenalysine,即使与竞争的 lysine.
- 成功的翻译后转换塞莱纳利到DHA.
- 证明了多不和和高度装饰的的制备.
结论:
- 已经建立了一种简单而强大的方法,通过核糖体合成生产含有脱氨酸的.
- 该方法允许生成各种库,具有潜在的治疗和诊断应用.
- 这种方法代表了在为药物发现和化学生物学工具创造蛋白质反应化合物的重大进步.
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