Tyramine fragment binding to BACE-1.
Basic Information
ID: ALA1142369
Journal: Bioorg Med Chem Lett
Title: Tyramine fragment binding to BACE-1.
Authors: Kuglstatter A, Stahl M, Peters JU, Huber W, Stihle M, Schlatter D, Benz J, Ruf A, Roth D, Enderle T, Hennig M.
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.
CiteXplore: 18226904
DOI: 10.1016/j.bmcl.2008.01.032
Patent ID: ┄