溶剂对prolyl键异构的能量学的影响
Eric S Eberhardt1, Stewart N Loh, Andrew P Hinck
1Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706.
Journal of the American Chemical Society
|April 1, 2011
概括
这项研究研究了溶剂中的键异构. 水比酸溶剂更多地增加了激活能量,影响了蛋白质的折叠和功能.
科学领域:
- 生物化学 生物化学
- 化学物理 化学物理
背景情况:
- 键异构化对于蛋白质的结构和功能至关重要.
- 了解溶剂对键动态的影响对于预测蛋白质行为至关重要.
研究的目的:
- 为了合成和描述一个模型Ac-Gly-[β,δ-(13) C]Pro-OMe.
- 在各种溶剂中确定prolyl键异构的动力学和热力学.
- 阐明溶剂性质的作用,如键和极性,在调节键异构化中的作用.
主要方法:
- 合成一个特定标记的类同类物.
- 核磁共振 (NMR) 谱学用于研究反应动力学.
- 红外 (IR) 光谱学用于分析热力学参数.
- 在九种不同的溶剂中进行动力学和热力学分析.
主要成果:
- 发现,在水中,同质化激活的自由能量相比,在性溶剂中显著更高 (1.3 kcal/mol的差异).
- 溶剂的键捐赠能力,而不是极性,与观察到的激活能量的变化相关.
- 结果支持胺共振模型,该模型涉及异构化过程中的电荷转移.
结论:
- 溶剂特性,特别是键捐赠,在键异构的能量学中起着至关重要的作用.
- 这些发现对理解基-基 cis-trans 同体酶 (PPIases) 的机制有意义.
- 对键稳定性的中等影响可能会影响蛋白质折叠,功能和降解过程.
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