Instituto de Productos Naturales y Agrobiología-CSIC, Avda. Astrofísico Francisco Sánchez, 3, 38206-La Laguna, Tenerife (Spain), Fax: (+34) 922-260135.
Chemistry. 2014 Apr 1;20(14):4007-22. doi: 10.1002/chem.201303841. Epub 2014 Feb 25.
New pyranoid ε-sugar amino acids were designed as building blocks, in which the carboxylic acid and the amine groups were placed in positions C2 and C3 with respect to the tetrahydropyran oxygen atom. By using standard solution-phase coupling procedures, cyclic homooligomers containing pyranoid ε-sugar amino acids were synthesized. Conformation analysis was performed by using NMR spectroscopic experiments, FTIR spectroscopic studies, X-ray analysis, and a theoretical conformation search. These studies reveal that the presence of a methoxy group in the position C4 of the pyran ring produces an important structural change in the cyclodipeptides. When the methoxy groups are present, the structure collapses through interresidue hydrogen bonds between the oxygen atoms of the pyran ring and the amide protons. However, when the cyclodipeptide lacks the methoxy groups, a U-shape structure is adopted, in which there is a hydrophilic concave face with four oxygen atoms and two amide protons directed toward the center of the cavity. Additionally, we found important evidence of the key role played by weak electrostatic interactions, such as the five-membered hydrogen-bonded pseudocycles (C5) between the amide protons and the ether oxygen atoms, in the conformation equilibrium of the macrocycles and in the cyclization step of the cyclic tetrapeptides.
新的吡喃糖 ε-氨基酸被设计为构建块，其中羧酸和胺基分别位于四氢吡喃氧原子的 C2 和 C3 位置。通过使用标准的溶液相偶联程序，合成了含有吡喃糖 ε-氨基酸的环状同寡聚物。通过 NMR 光谱实验、FTIR 光谱研究、X 射线分析和理论构象搜索进行构象分析。这些研究表明，吡喃环 C4 位置的甲氧基的存在会导致环二肽发生重要的结构变化。当存在甲氧基时，结构通过吡喃环的氧原子和酰胺质子之间的分子内氢键坍塌。然而，当环二肽缺乏甲氧基时，会采用 U 形结构，其中有一个亲水的凹面，四个氧原子和两个酰胺质子指向空腔的中心。此外，我们发现了重要证据，证明弱静电相互作用（如酰胺质子和醚氧原子之间的五元氢键环（C5））在大环的构象平衡和环状四肽的环化步骤中起着关键作用。
