Liu Yu, Yang Ying-Wei, Chen Yong, Ding Fei
Department of Chemistry, State Key Laboratory of Elemento-Organic Chemistry, Nankai University, Tianjin 300071, PR China.
Bioorg Med Chem. 2005 Feb 15;13(4):963-71. doi: 10.1016/j.bmc.2004.11.042.
Two 6,6'-bis(beta-cyclodextrin)s linked by 2,2'-dithiobis[2-(benzoylamino)ethyleneamino] and 2,2'-dithiobis[2-(benzoylamino)diethylenetriamino] bridges (1 and 2) have been synthesized as cooperative multipoint recognition receptor models for non-aromatic oligopeptides. Their structures in solution and inclusion complexation mechanism are comprehensively investigated by means of circular dichroism, 2D NMR spectra and temperature-dependent fluorescence titrations. The results show that the cooperative 'host-linker-guest' binding mode and the extensive desolvation effect jointly contribute to the guest-induced fluorescence enhancement of bis(beta-cyclodextrin)s. Further examinations on the binding behavior of hosts 1-2 with a series of di- and tri-peptides demonstrate that bis(beta-cyclodextrin) 1 can recognize not only the size/shape of oligopeptides but also the dipeptide sequence, giving an exciting residue selectivity up to 37.5 for Gly-Gly-Gly/Glu-Glu pair and a high sequence selectivity up to 5.0 for Gly-Leu/Leu-Gly pair. These fairly good selectivities are discussed from the viewpoint of cooperative binding, multiple recognition and induced-fit interactions between host and guest.
通过2,2'-二硫代双[2-(苯甲酰氨基)乙烯氨基]和2,2'-二硫代双[2-(苯甲酰氨基)二亚乙基三氨基]桥连接的两个6,6'-双(β-环糊精)(1和2)已被合成为非芳香族寡肽的协同多点识别受体模型。通过圆二色性、二维核磁共振光谱和温度依赖性荧光滴定对它们在溶液中的结构和包合络合机制进行了全面研究。结果表明，协同的“主体-连接体-客体”结合模式和广泛的去溶剂化效应共同导致了双(β-环糊精)客体诱导的荧光增强。对主体1-2与一系列二肽和三肽的结合行为的进一步研究表明，双(β-环糊精)1不仅可以识别寡肽的大小/形状，还可以识别二肽序列，对于甘氨酰-甘氨酰-甘氨酸/谷氨酸-谷氨酸对，残基选择性高达37.5，对于甘氨酰-亮氨酸/亮氨酸-甘氨酸对，序列选择性高达5.0。从主体与客体之间的协同结合、多重识别和诱导契合相互作用的角度讨论了这些相当好的选择性。
