合作性分子内结强化折叠
Andrew W Wijaya1, Andy I Nguyen1, Leah T Roe1
1The Molecular Foundry , Lawrence Berkeley National Laboratory , 1 Cyclotron Road , Berkeley , California 94720 , United States.
Journal of the American Chemical Society
|November 26, 2019
概括
研究人员开发了新的阴离子侧链,通过强制执行cis-amide形状来控制状折叠. 这一突破使得精确结构的折叠形序列可以用于各种应用.
科学领域:
- 聚合物化学
- 超分子化学
- 生物材料科学
背景情况:
- 类 (N替代型甘氨酸) 提供生物稳定性和合成优势,但缺乏精确的3D结构控制.
- 控制体骨干构造,特别是cis-amide异构化,对于折叠结构的新设计至关重要.
研究的目的:
- 开发能够决定性地控制形骨形状的新型侧链.
- 为了使精确定义的,折叠的形结构用于先进的应用.
主要方法:
- 新型阳基乙烯侧链的合成.
- 使用X射线结晶学,可变温度NMR光谱学和DFT计算进行表征.
- 通过多维NMR光谱测定水溶性类10-mer的固体相合成.
主要成果:
- 阴离子侧链通过分子内结合有效地强制执行cis-amide骨干构成 (Kd高达70).
- 这些侧链是廉价的,多样化的,水友性的,并且与固相合成相容.
- 合成了10-mer形序列,在溶液中表现出主要的折叠,代表了最长的原子特征折叠线性形.
结论:
- 新型侧链为控制形折叠提供了关键工具,并使精确的3D结构设计成为可能.
- 这种进步克服了体折叠的一个主要障碍,为新的应用铺平了道路.
- 这些发现预计将对制药和材料科学领域产生重大影响.
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