title: Macrocyclic peptidomimetic inhibitors of beta-secretase (BACE): first X-ray structure of a macrocyclic peptidomimetic-BACE complex.
abstract: The synthesis of novel macrocyclic peptidomimetic inhibitors of the enzyme BACE1 is described. These macrocycles are derived from a hydroxyethylene core structure. Compound 7 was co-crystallized with BACE1 and the X-ray structure of the complex elucidated at 1.6 Angstrom resolution. This molecule inhibits the production of the Abeta peptide in HEK293 cells overexpressing APP751sw.
authors.affiliation: Lilly S.A., Avenida de la Industria 30, 28108 Alcobendas, Spain. irojo@lilly.com
authors.forename: Isabel
authors.initials: I
authors.lastname: Rojo
authors.forename: José Alfredo
authors.initials: JA
authors.lastname: Martín
authors.forename: Howard
authors.initials: H
authors.lastname: Broughton
authors.forename: David
authors.initials: D
authors.lastname: Timm
authors.forename: Jon
authors.initials: J
authors.lastname: Erickson
authors.forename: Hsiu-Chiung
authors.initials: HC
authors.lastname: Yang
authors.forename: James R
authors.initials: JR
authors.lastname: McCarthy
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases; D016564:Amyloid beta-Protein Precursor / Q000737:chemistry; D000818:Animals; D016282:Aspartic Acid Endopeptidases; D002460:Cell Line; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D018360:Crystallography, X-Ray / Q000379:methods*; D015195:Drug Design; D010450:Endopeptidases / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D011487:Protein Conformation; D017434:Protein Structure, Tertiary
chemical_list: D016564:Amyloid beta-Protein Precursor; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human