title: Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase.
abstract: Gamma-secretase is the second of two proteolytic enzymes responsible for the release of the amyloid beta-peptide implicated in the etiology of Alzheimer's disease. Here, we used solid-phase synthesis to generate a new series of helical peptides as gamma-secretase inhibitors, one of which, 11, showed an IC(50) of 140 pM in a cell-free enzyme assay.
authors.affiliation: Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Bihel
authors.forename: Chittaranjan
authors.initials: C
authors.lastname: Das
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bowman
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wolfe
mesh_terms: D053829:Amyloid Precursor Protein Secretases; D002942:Circular Dichroism; D010450:Endopeptidases / Q000737:chemistry*; D010455:Peptides / Q000138:chemical synthesis* / Q000737:chemistry; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D017433:Protein Structure, Secondary; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D010455:Peptides; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases