Department of Life Science and Chemistry, Graduate School of Natural Science and Technology, Gifu University, 1-1 Yanagido, Gifu 501-1193, Japan.
Org Biomol Chem. 2018 Nov 14;16(44):8505-8512. doi: 10.1039/c8ob01962b.
Macrocyclic peptide-mimetic molecules are attracting renewed attention and have found widespread application in research fields ranging from biochemical science to materials science. Herein, we describe the synthesis and structural elucidation of cyclo[n]-p-arylopeptoids (classified into cyclic aromatic ε-amino acids) bearing various side chains, namely, C[n]pAP(Rn) (where n inside brackets denotes the number of main chain units and R inside parentheses represents side chains). We investigate the influence of n and R on the macrocyclization efficiency of linear p-arylopeptoid oligomers (n = 3, 4, 5) under high-dilution conditions with or without slow addition. The structures of the cyclo[4]-p-arylopeptoids (C[4]pAP(Rn)) and their conformational dynamics are disclosed on the basis of single-crystal X-ray analyses, viable-temperature (VT) 1H NMR studies, and density functional theory (DFT) calculations. We found two representative conformations (open and closed) of cyclo[4]-p-arylopeptoids (C[4]pAP(Rn)) in the solid state and whose preference in the solution state was most likely dependent on solvent polarity. We believe that this simple but dynamic macrocyclic peptide-mimetic molecular scaffold would be attractive for developing new functional molecular tools based on rational molecular design as well as molecular library screening strategies.
大环肽模拟分子重新引起了人们的关注，并在从生化科学到材料科学等研究领域得到了广泛的应用。在此，我们描述了具有各种侧链的环[n]-p-芳基肽拟肽（分类为环状芳香族ε-氨基酸）的合成和结构阐明，即 C[n]pAP(Rn)（其中方括号内的 n 表示主链单元的数量，圆括号内的 R 表示侧链）。我们研究了 n 和 R 对在高稀释条件下（有或没有缓慢添加）线性 p-芳基肽寡聚物（n = 3、4、5）的大环化效率的影响。基于单晶 X 射线分析、可行温度（VT）1H NMR 研究和密度泛函理论（DFT）计算，揭示了环[4]-p-芳基肽拟肽（C[4]pAP(Rn))的结构和构象动力学。我们在固态中发现了两种代表性的环[4]-p-芳基肽拟肽（C[4]pAP(Rn))构象（开环和闭环），其在溶液状态下的偏好可能取决于溶剂极性。我们相信，这种简单但动态的大环肽模拟分子支架将很有吸引力，可用于基于合理分子设计以及分子文库筛选策略开发新的功能分子工具。
