Abstract
A rationally designed oligomerization inhibitor interacts with early intermediate assemblies of amyloid-beta polypeptide (Abeta) through the aromatic elements and inhibits their assembly into the toxic oligomers that cause Alzheimer's disease by a unique C(alpha)-methylation beta-breakage strategy. The electrostatic potential of the low-energy conformation of the dipeptide inhibitor bound to Abeta is shown.
MeSH terms
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Alzheimer Disease / drug therapy*
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Amyloid beta-Peptides / chemistry*
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Amyloid beta-Peptides / metabolism
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Animals
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Blood-Brain Barrier
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Cell Line
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Dipeptides / chemistry
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Dipeptides / pharmacology*
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Dipeptides / therapeutic use
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Disease Models, Animal
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Fluorescence Polarization
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Magnetic Resonance Spectroscopy
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Mice
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Mice, Transgenic
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PC12 Cells
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Rats
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Static Electricity
Substances
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Amyloid beta-Peptides
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Dipeptides