Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1373032 | Bioorganic & Medicinal Chemistry Letters | 2008 | 4 Pages |
Abstract
Fragment screening revealed that tyramine binds to the active site of the Alzheimer’s disease drug target BACE-1. Hit expansion by selection of compounds from the Roche compound library identified tyramine derivatives with improved binding affinities as monitored by surface plasmon resonance. X-ray structures show that the amine of the tyramine fragment hydrogen-bonds to the catalytic water molecule. Structure-guided ligand design led to the synthesis of further low molecular weight compounds that are starting points for chemical leads.
Graphical abstractTyramine and derivatives thereof bind to the active site of the Alzheimer’s disease drug target BACE-1.Figure optionsDownload full-size imageDownload as PowerPoint slide
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Andreas Kuglstatter, Martin Stahl, Jens-Uwe Peters, Walter Huber, Martine Stihle, Daniel Schlatter, Jörg Benz, Armin Ruf, Doris Roth, Thilo Enderle, Michael Hennig,