PUBLICATION
Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor
- Authors
- Li, S., Chen, H., Yang, X., Bardelang, D., Wyman, I.W., Wan, J., Lee, S.M., Wang, R.
- ID
- ZDB-PUB-151230-6
- Date
- 2015
- Source
- ACS Medicinal Chemistry Letters 6: 1174-8 (Journal)
- Registered Authors
- Keywords
- Neurodegeneration, cucurbituril, inhibition, neurotoxin, supramolecular complexation
- MeSH Terms
- none
- PubMed
- 26713100 Full text @ ACS Med. Chem. Lett.
Citation
Li, S., Chen, H., Yang, X., Bardelang, D., Wyman, I.W., Wan, J., Lee, S.M., Wang, R. (2015) Supramolecular Inhibition of Neurodegeneration by a Synthetic Receptor. ACS Medicinal Chemistry Letters. 6:1174-8.
Abstract
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 (1)H 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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping