改变形状的核化物 - - 柔性聚合物的构造性质
Matjaz Polak1, Katherine L Seley, Janez Plavec
1Slovenian NMR Center, National Institute of Chemistry, Hajdrihova 19, POB 660, SI-1001 Ljubljana, Slovenia.
Journal of the American Chemical Society
|July 1, 2004
概括
柔性核酸因柔性核基而表现出增加的抗构成和北型糖构成. 这些发现对于设计针对灵活结合点的形状模拟核化物至关重要.
科学领域:
- 药用化学 医学化学
- 有机化学 有机化学
- 计算化学的计算化学
背景情况:
- 自然核酸是DNA和RNA的重要组成部分.
- 了解核酸构成是药物设计的关键.
- 柔性核化物为潜在的治疗应用提供了改性结构.
研究的目的:
- 为了研究柔性分子核酸的溶液状态结构.
- 为了比较柔性核酸与自然对应物的构造性质.
- 阐明控制核体构成的立体电子因素.
主要方法:
- 溶液状态的 (1) H 核磁共振 ((1) H NMR) 光谱学.
- 一开始的计算化学.
- 核糖类相似物的一致性分析.
主要成果:
- 与天然核酸相比,柔性核酸显示出环绕糖酸结合的反形状的显著较高的人口.
- 在柔性核酸中观察到明显的朝向北型糖的转变.
- 核基部分之间的键和有利的结合被确定为影响构造的关键因素.
结论:
- 核基的灵活性和立体电子效应极大地影响了核酸的构成.
- 柔性核化物表现出明显的结构偏好,可以在药物发现中加以利用.
- 这些发现指导了与灵活的生物标相互作用的新型核类相应物的合理设计.
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