Graduate School of Pharmaceutical Sciences , University of Tokyo , 7-3-1 Hongo , Bunkyo-ku , Tokyo 113-0033 , Japan.
Research Foundation Itsuu Laboratory , C1232 Kanagawa Science Park R&D Building, 3-2-1 Sakado, Takatsu-ku , Kawasaki , Kanagawa 213-0012 , Japan.
Org Lett. 2019 Oct 4;21(19):7813-7817. doi: 10.1021/acs.orglett.9b02799. Epub 2019 Sep 13.
Our NMR, IR/Raman, CD spectroscopic, and X-ray crystallographic studies, as well as accelerated molecular dynamics simulations, showed that alternating hybrid α/β-peptides containing a bicyclic β-proline surrogate form unique extended curved folds, regardless of the peptide length and solvent environment. It is suggested that extended β/PPII structures are preferred in the insulating α-alanine moieties between the rigid bicyclic β-proline structures. These hybrid peptides inhibit p53-MDM2 and p53-MDMX protein-protein interactions.
我们的 NMR、IR/Raman、CD 光谱和 X 射线晶体学研究，以及加速分子动力学模拟表明，无论肽的长度和溶剂环境如何，含有双环 β-脯氨酸类似物的交替混合α/β-肽形成独特的扩展弯曲折叠。这表明，在刚性双环β-脯氨酸结构之间的绝缘α-丙氨酸部分中，优先形成扩展的β/PPII 结构。这些混合肽抑制 p53-MDM2 和 p53-MDMX 蛋白-蛋白相互作用。
