在人类二氧化碳无酶II的晶格中结合的抑制剂之间的芳-芳相互作用
1Roy and Diana Vagelos Laboratories, Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104-6323, USA.
Journal of the American Chemical Society
|September 27, 2001
概括
在芳香抑制剂上的替代影响了它们的晶体包装. 特定的模式促进面对面或原子对面的相互作用,由伦敦力和电荷转移驱动.
科学领域:
- 生物化学 生物化学
- 化学晶体学 化学晶体学
- 药用化学 医学化学
背景情况:
- 碳酸无水酶II是生物系统中至关重要的酶.
- 芳香化合物正在作为潜在的酶抑制剂进行研究.
- 了解分子间相互作用是药物设计的关键.
研究的目的:
- 研究替代如何影响二氧化碳无水酶II的抑制剂的分子间相互作用.
- 分析抑制剂结合和包装的结构基础.
- 阐明控制芳环协会的主导力量.
主要方法:
- 通过X射线晶体学,用11种芳醇抑制剂来确定二氧化碳无水酶II的晶体结构.
- 分析晶格内部的分子间相互作用.
- 范德瓦尔斯效应,静电效应和电荷转移效应的计算分析.
主要成果:
- 替代的程度和模式调节了抑制剂的大小,形状和电子特性.
- 观察到的相互作用包括面对面 (芳香-芳香) 和原子对面 (碳烯-芳香).
- 伦敦分散力和电荷转移复杂化被发现在芳香环协会中的静电相互作用中占主导地位.
结论:
- 化模式极大地影响了水晶格子中芳香抑制剂的自我组装.
- 这些发现为设计具有优化的结合相互作用的酶抑制剂提供了洞察力.
- 突出了伦敦力的主导地位和芳香对协会中的电荷转移.
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