Macrocyclic Statine-Based Inhibitors of BACE-1 (pages 2078–2091)
Alessandra Barazza, Marion Götz, Sergio A. Cadamuro, Peter Goettig, Michael Willem, Holger Steuber, Tanja Kohler, Anja Jestel, Peter Reinemer, Christian Renner, Wolfram Bode and Luis Moroder
Version of Record online: 26 OCT 2007 | DOI: 10.1002/cbic.200700383
Hitting BACE. A 23-membered macrocyclic inhibitor of BACE-1 containing statine as a transition state analogue in the ring structure (green) was found to bind with the peptide backbone in an extended conformation to the active-site cleft, in a manner almost identical to that of a substrate-derived linear hydroxyethylene-octapeptide (yellow), without steric clashes with the flap domain.