An In-tether Chiral Center Modulates the Helicity, Cell Permeability, and Target Binding Affinity of a Peptide
An In-tether Chiral Center Modulates the Helicity, Cell Permeability, and Target Binding Affinity of a Peptide
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链内手性中心调节肽的螺旋度、细胞渗透性和目标结合亲和力
DOI：
10.1002/anie.201602806
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发表时间：
2016-07-04
影响因子：
16.6
通讯作者：
Li, Zigang
中科院分区：
文献类型：
--
作者：
Hu, Kuan;Geng, Hao;Li, Zigang
通过圆二色谱(CD)和核磁共振波谱的研究，发现在一个受约束的多肽的链段上增加了一个精确定位的手性中心，得到了两个螺旋度明显不同的可分离多肽非对映异构体。单晶X-射线衍射分析表明，绳内手性中心螺旋形的绝对构型为R，这与理论模拟相一致。短肽的二级结构和它们的生化/生物物理性质之间的关系仍然难以捉摸，这主要是因为缺乏适当的控制。本方法为研究构象差异对多肽生化/生物物理性质的影响提供了唯一的方法。多肽非对映异构体之间在通透性和靶向结合亲和力方面的显著差异表明了螺旋构象的重要性。
The addition of a precisely positioned chiral center in the tether of a constrained peptide is reported, yielding two separable peptide diastereomers with significantly different helicity, as supported by circular dichroism (CD) and NMR spectroscopy. Single crystal X-ray diffraction analysis suggests that the absolute configuration of the in-tether chiral center in helical form is R, which is in agreement with theoretical simulations. The relationship between the secondary structure of the short peptides and their biochemical/biophysical properties remains elusive, largely because of the lack of proper controls. The present strategy provides the only method for investigating the influence of solely conformational differences upon the biochemical/biophysical properties of peptides. The significant differences in permeability and target binding affinity between the peptide diastereomers demonstrate the importance of helical conformation.