School of Chemical Biology and Biotechnology, Peking University Shenzhen Graduate School, Shenzhen, 518055, China.
Department of Biology, Southern University of Science and Technology, Shenzhen, 518055, China.
Angew Chem Int Ed Engl. 2016 Jul 4;55(28):8013-7. doi: 10.1002/anie.201602806. Epub 2016 May 11.
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.
据报道，在约束肽的连接物中加入一个精确定位的手性中心，生成两种可分离的肽非对映异构体，其螺旋性有显著差异，这得到圆二色性（CD）和核磁共振（NMR）光谱的支持。单晶 X 射线衍射分析表明，螺旋形式中连接物上手性中心的绝对构型为 R，这与理论模拟一致。短肽的二级结构与其生化/生物物理特性之间的关系仍然难以捉摸，主要是因为缺乏适当的对照。本研究策略为仅通过构象差异来研究其对肽的生化/生物物理性质的影响提供了唯一的方法。肽非对映异构体在通透性和靶标结合亲和力方面的显著差异证明了螺旋构象的重要性。
