在Bradykinin中对形调节的键裂变
Daniel R Fuller1, Christopher R Conant1, Tarick J El-Baba1
1Department of Chemistry , Indiana University , Bloomington , Indiana 47405 , United States.
Journal of the American Chemical Society
|July 21, 2018
概括
布拉迪基宁 (BK) 在 Pro2-Pro3 键处经历独特的非酶分裂,由温度诱导的质子化和异构化触发. 这种内在的途径对人体酶具有抗性,为处理和抗原性提供了洞察力.
科学领域:
- 生物化学
- 化学物理
- 分析化学
背景情况:
- 布拉迪基宁 (BK) 是一种具有已知的生物功能的.
- 了解的稳定性和加工对于药物开发和生物研究至关重要.
- 内在裂路径可以提供对生物抵抗机制的见解.
研究的目的:
- 使用离子移动性和质谱学研究不同布拉迪基宁 (BK) 构造的构造稳定性.
- 在BK中阐明一种新的非酶性Pro2-Pro3键裂的机制.
- 确定BK处理所涉及的过渡状态的热力学参数.
主要方法:
- 离子运动谱与质谱相结合 (IM-MS).
- 温度依赖的运动研究.
- 对质子反应和形状变化的分析.
主要成果:
- 高温诱导缓慢的质子反应 ([BK+2H]2+ → [BK+3H]3+) 通过Arg1-Pro2转化 → cis异构化进行调节.
- 全cis [BK+3H]3+ 构造自发地以高特异性裂解了 Pro2-Pro3 键.
- 这种裂变通过多种中间体发生,由Arg1-Pro2异构化调节,并且具有生物耐药性.
- 确定了质子化和键裂变的过渡状态热化学.
结论:
- 在Pro2-Pro3键上确定了布拉迪基宁的新型非酶裂解途径.
- 这一途径由Arg1-Pro2 trans → cis异构和质子化调节.
- 对这种内在加工途径的生物耐药性对抗原性有影响.
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