§Center for Self-Assembly and Complexity, Institute for Basic Science, Pohang University of Science and Technology (POSTECH), Pohang 790-784, Republic of Korea.
J Phys Chem B. 2015 Apr 2;119(13):4628-36. doi: 10.1021/acs.jpcb.5b00743. Epub 2015 Mar 19.
This work presents a systematic study on the host-guest interactions between the macrocyclic host molecule cucurbit[7]uril (CB[7]) and amino acids (AAs) including three basic AAs (Lys, Arg, and His) and three aromatic AAs (Phe, Tyr, and Trp) to elucidate the origin of the high selectivity of CB[7] toward AA residues in proteins. Complex formation between CB[7] and each AA was examined in solution (by isothermal titration calorimetry and NMR) as well as in the gas phase (by ion mobility mass spectrometry and collision-induced dissociation), and the results were further combined with computational investigations. Generally, the aromatic AAs show higher binding affinities than the basic AAs in buffer solutions with various pH values. On the contrary, the gas-phase stabilities of the basic AA complex ions are higher than those of the aromatic AA complex ions, suggesting that the direct ion-dipole interactions between the charged side chains of the basic AAs and the polar carbonyl groups of CB[7] predominate in the absence of water. The ion-dipole interactions are less significant in water, since the original interactions of the guests with water are lost upon complex formation. In contrast, the transfer of the hydrophobic groups from the bulk into the hydrophobic CB[7] cavity suffers less from the desolvation penalty, resulting in higher binding affinities in water. Therefore, initial guest solvation is another key factor which should be considered when designing high-affinity host-guest systems, in addition to the contribution from the release of high-energy water molecules from the CB[7] cavity (J. Am. Chem. Soc. 2012, 134, 15318-15323).
这项工作系统研究了大环主体分子葫芦脲（CB[7]）与氨基酸（AAs）之间的主客体相互作用，包括三种碱性氨基酸（Lys、Arg 和 His）和三种芳香族氨基酸（Phe、Tyr 和 Trp），以阐明 CB[7]对蛋白质中 AA 残基具有高选择性的起源。通过等温滴定微量热法和 NMR 在溶液中以及通过离子淌度质谱和碰撞诱导解离在气相中检查了 CB[7]与每种 AA 之间的配合物形成，并将结果与计算研究进一步结合。通常，在各种 pH 值的缓冲溶液中，芳香族氨基酸的结合亲和力高于碱性氨基酸。相反，在气相中，碱性 AA 配合物离子的稳定性高于芳香族 AA 配合物离子的稳定性，这表明在没有水的情况下，带电荷的碱性 AA 侧链与 CB[7]的极性羰基之间的直接离子偶极相互作用占主导地位。在水中，离子偶极相互作用不太重要，因为在形成配合物时，客体与水的原始相互作用会丢失。相反，疏水性基团从本体转移到疏水性 CB[7]腔中受到的去溶剂化惩罚较小，导致在水中结合亲和力更高。因此，除了从 CB[7]腔中释放高能水分子的贡献外，客体的初始溶剂化也是设计高亲和力主客体体系时应考虑的另一个关键因素（J. Am. Chem. Soc. 2012, 134, 15318-15323）。
