ABSTRACT The binding of 1 and 2 toward 19 amino acid amides by 1H NMR and ITC is reported. Hosts 1 and 2 bind to aromatic or hydrophobic residues by cavity inclusion leaving the cationic residues at the C=O portals. Ka values range from 102 to >106 M−1 with H-Phe-NH2, H-Trp-NH2, and H-Tyr-NH2 displaying sub-micromolar Kd values. Hosts 1 and 2 bind tightly to dicationic H-Lys-NH2 and H-Arg-NH2 which are poor guests for CB[7]. Comparison of the affinity of 1 and 2 toward the amino acid amide, N-acetyl-amino-acid amide, and amino acid forms of Phe revealed that the removal of the NH3+ to O=C and SO3− electrostatic interactions costs 3.8 kcal/mol whereas the introduction of an unfavourable CO2− to O=C and SO3− electrostatic interactions costs 2.1 kcal/mol. Hosts 1 and 2 bind to insulin with low micromolar affinity. Acyclic CB[n] display high affinity toward a wider range of N-terminal amino acids residues than CB[n] which suggests a broad range of applications. Graphical Abstract Table of contents graphic

中文翻译：

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无环葫芦脲对氨基酸、肽和蛋白质的分子识别特性

摘要 1H NMR 和 ITC 报道了 1 和 2 与 19 个氨基酸酰胺的结合。宿主 1 和 2 通过空腔包含与芳香族或疏水性残基结合，将阳离子残基留在 C=O 入口处。Ka 值范围从 102 到 >106 M-1，其中 H-Phe-NH2、H-Trp-NH2 和 H-Tyr-NH2 显示亚微摩尔 Kd 值。宿主 1 和 2 与双阳离子 H-Lys-NH2 和 H-Arg-NH2 紧密结合，它们是 CB 的不良客体 [7]。比较 1 和 2 对氨基酸酰胺、N-乙酰氨基酸酰胺和 Phe 氨基酸形式的亲和力表明，将 NH3+ 去除到 O=C 和 SO3− 静电相互作用的成本为 3.8 kcal/mol而将不利的 CO2− 引入 O=C 和 SO3− 静电相互作用的成本为 2.1 kcal/mol。宿主 1 和 2 以低微摩尔亲和力与胰岛素结合。与 CB[n] 相比，无环 CB[n] 对更广泛的 N 端氨基酸残基显示出高亲和力，这表明其应用范围很广。图形摘要目录图形