Deciphering the Specific High-Affinity Binding of Cucurbit[7]uril to Amino Acids in Water
Deciphering the Specific High-Affinity Binding of Cucurbit[7]uril to Amino Acids in Water
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DOI：
10.1021/acs.jpcb.5b00743
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发表时间：
2015-04-02
影响因子：
3.3
通讯作者：
Kim, Hugh I.
中科院分区：
文献类型：
--
作者：
Lee, Jong Wha;Lee, Hyun Hee L.;Kim, Hugh I.
本文系统地研究了大环主体分子葫芦[7]脲（CB[7]）与三种碱性氨基酸（Lys、Arg、His）和三种芳香族氨基酸（Phe、Tyr、Trp）之间的主客体相互作用，以阐明CB[7]对蛋白质中氨基酸残基具有高选择性的原因。CB[7]和每个AA之间的复合物形成在溶液中（通过等温滴定量热法和NMR）以及在气相中（通过离子迁移率质谱和碰撞诱导解离）进行了检查，结果进一步与计算研究相结合。在不同pH值的缓冲溶液中，芳香族氨基酸的结合亲和力普遍高于碱性氨基酸。相反，碱性AA络合物离子的气相稳定性高于芳香族AA络合物离子的气相稳定性，这表明在不存在水的情况下，碱性AA的带电侧链与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。离子-偶极相互作用在水中不太显著，因为客体与水的原始相互作用在络合物形成时丧失。相比之下，疏水基团从本体转移到疏水CB[7]腔中受到的去溶剂化惩罚较小，导致在水中的结合亲和力较高。因此，初始客体溶剂化是在设计高亲和力主体-客体系统时应当考虑的另一个关键因素，除了来自CB[7]腔释放的高能水分子的贡献之外（J. Am. 2012，134，15318-15323）。
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).