Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University.
Chem Pharm Bull (Tokyo). 2021;69(6):585-589. doi: 10.1248/cpb.c21-00047.
The addition of an aqueous solution of diketopiperazine cyclo(Pro-Xxx) (Xxx: amino acid residue) to an aqueous solution of (-)-epigallocatechin-3-O-gallate (EGCg) led to precipitation of the complex of EGCg and cyclo(Pro-Xxx). The molecular capture abilities of cyclo(Pro-Xxx) using EGCg were evaluated by the ratio of the amount of cyclo(Pro-Xxx) included in the precipitates of the complex with EGCg to that of the total cyclo(Pro-Xxx) used. Stronger hydrophobicity of the side chain of the amino acid residue of cyclo(Pro-Xxx) led to a higher molecular capture ability. Furthermore, the molecular capture ability decreased when the side chain of the amino acid residue had a hydrophilic hydroxyl group. When diketopiperazine cyclo(Pro-Xxx), excluding cyclo(D-Pro-L-Ala), was taken into the hydrophobic space formed by the three aromatic A, B, and B' rings of EGCg, and formed a complex, their conformation was maintained in the hydrophobic space. Based on nuclear Overhauser effect (NOE) measurement, the 3-position methyl group of cyclo(D-Pro-L-Ala) in DO was axial, whereas that of cyclo(L-Pro-L-Ala) was equatorial. When cyclo(D-Pro-L-Ala) was taken into the hydrophobic space of EGCg and formed a 2 : 2 complex, its 3-position methyl group changed from the axial position to the equatorial position due to steric hindrance by EGCg.
将二酮哌嗪环（Pro-Xxx）（Xxx：氨基酸残基）的水溶液加入到（-）-表没食子儿茶素-3-O-没食子酸酯（EGCg）的水溶液中，导致 EGCg 与环（Pro-Xxx）的复合物沉淀。通过 EGCg 中环（Pro-Xxx）的量与所用总环（Pro-Xxx）的量之比，评估了环（Pro-Xxx）与 EGCg 形成的复合物中环（Pro-Xxx）的分子捕获能力。环（Pro-Xxx）侧链的疏水性越强，分子捕获能力越强。此外，当氨基酸残基的侧链具有亲水性的羟基时，分子捕获能力降低。当二酮哌嗪环（Pro-Xxx）（不包括环（D-Pro-L-Ala））进入 EGCg 的三个芳香 A、B 和 B'环形成的疏水区，并形成复合物时，它们的构象在疏水区得以保持。基于核 Overhauser 效应（NOE）测量，DO 中环（D-Pro-L-Ala）的 3 位甲基呈轴向，而环（L-Pro-L-Ala）的 3 位甲基呈平伏键。当环（D-Pro-L-Ala）进入 EGCg 的疏水区并形成 2：2 复合物时，由于 EGCg 的空间位阻，其 3 位甲基从轴向位置变为平伏键位置。
