Abstract
The stereoselective synthesis of novel photoreactive gamma-secretase inhibitors 2 and 3 has been achieved. Key steps of the strategy involve preparation of alpha-N-Boc-epoxide 8 and formation of lactone 14 in a practical and stereo-controlled fashion. Compounds 2 and 3 are potent gamma-secretase inhibitors and directly interact with presenilin-1, a catalytic subunit of gamma-secretase.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / metabolism
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Amyloid Precursor Protein Secretases / antagonists & inhibitors*
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Amyloid Precursor Protein Secretases / metabolism
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Biotinylation
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Crystallography, X-Ray / methods
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Dipeptides / chemistry
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Drug Design
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Epoxy Compounds / chemistry
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HeLa Cells
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Humans
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Inhibitory Concentration 50
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Lactones / chemistry
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Models, Chemical
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Photochemistry / methods
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Presenilin-1 / chemistry
Substances
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Dipeptides
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Epoxy Compounds
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Lactones
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Presenilin-1
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Amyloid Precursor Protein Secretases