Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor
Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor
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DOI：
10.1021/acsmedchemlett.5b00372
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发表时间：
2015-12-01
影响因子：
4.2
通讯作者：
Wang, Ruibing
中科院分区：
文献类型：
--
作者：
Li, Shengke;Chen, Huanxian;Wang, Ruibing
葫芦[7]脲 (CB[7]) 在体外被发现可以隔离神经毒素 MPTP（N-甲基-4-苯基-1,2,3,6-四氢吡啶）和 MPP+（N-甲基-4-苯基吡啶）。利用 H-1 NMR、电喷雾电离质谱、紫外-可见光谱滴定和密度泛函理论分子建模对 CB[7]/神经毒素主客体复合物进行了详细研究。结果支持CB[7]在水溶液中分别对MPTP和MPP+进行大环封装，在两种情况下具有相对强的亲和力和1:1的主客体结合化学计量。更重要的是，如斑马鱼模型所示，观察到 MPTP/MPP+ 诱导的神经变性（通常称为帕金森病模型）的进展在体内受到合成 CB[7] 受体的强烈抑制。这些结果表明，超分子方法可能会产生新的预防和/或治疗策略，以抵消某些神经毒素导致神经变性的有害影响。
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-guest complexes were studied in detail with H-1 NMR, electrospray ionization mass spectrometry, UV-visible 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-guest binding stoichiometries in both cases. More importantly, the progression of MPTP/MPP+ induced neurodegeneration (often referred to as a Parkinson's 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.