一种对iboxamycin的三度化方法允许测量其核糖体结合的方法
Kelvin J Y Wu1, Dorota Klepacki2, Alexander S Mankin2
1Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Bioorganic & medicinal chemistry letters
|June 9, 2023
概括
研究人员开发了一种新的方法来对抗生素伊博克萨米进行三标记,克服了以前技术的局限性. 由此产生的三标记的伊博克萨米对大肠杆菌核糖体具有强烈的活性.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 生物化学 生物化学
背景情况:
- -交换是放射性同位素标记的一个常见方法.
- 传统的方法仅限于sp2杂交的碳键,不适合像iboxamycin这样的分子.
- 开发新的标签策略对于研究复杂的生物分子至关重要.
研究的目的:
- 开发一种用于三标记iboxamycin的新方法.
- 描述标记的化合物的放射性同位素特性和特异性活性.
- 评估iboxamycin对细菌核糖体的生物活性.
主要方法:
- 在HTO中诱导2'-epi-iboxamycin的鲁诱导的2'-epimerization.
- 净化标有三标记的iboxamycin. 这是一个非常好的方法.
- 对大肠杆菌核糖体的特定活性和抑制常数 (Ki,app) 的测量.
主要成果:
- 成功合成了标有三的伊博克萨米,其特异活性为53mCi/mmol.
- 伊博克萨米辛证明了埃舍里希亚大肠杆菌核糖体的强烈抑制,其Ki,app为41±30nM.
- 与克林达米辛相比,伊博克萨米辛的结合亲和力大约是70倍.
结论:
- 催化2'-epimerization提供了一个有效的途径,以三标记的iboxamycin.
- 标有三标签的伊博克萨米是进一步生物研究的宝贵工具.
- 伊博克萨米是一种强大的细菌核糖体功能的抑制剂.
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