Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor

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• 作者：Shengke Li ; Huanxian Chen ; Xue Yang ; David Bardelang ; Ian W. Wyman ; Jianbo Wan ; Simon M. Y. Lee ; Ruibing Wang
• 刊名：ACS Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：December 10, 2015
• 年：2015
• 卷：6
• 期：12
• 页码：1174-1178
• 全文大小：341K
• ISSN：1948-5875

文摘

Cucurbit[7]uril (CB[7]) was found in vitro to sequester the neurotoxins MPTP (N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and MPP⁺ (N-methyl-4-phenylpyridine). The CB[7]/neurotoxin host鈥揼uest complexes were studied in detail with ¹H NMR, electrospray ionization mass spectrometry, UV鈥搗isible spectroscopic titration, and molecular modeling by density functional theory. The results supported the macrocyclic encapsulation of MPTP and MPP⁺, respectively, by CB[7] in aqueous solutions with relatively strong affinities and 1:1 host鈥揼uest binding stoichiometries in both cases. More importantly, the progression of MPTP/MPP⁺ induced neurodegeneration (often referred to as a Parkinson鈥檚 disease model) was observed to be strongly inhibited in vivo by the synthetic CB[7] receptor, as shown in zebrafish models. These results show that a supramolecular approach could lead to a new preventive and/or therapeutic strategy for counteracting the deleterious effects of some neurotoxins leading to neurodegeneration.