Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase.
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.
Bihel
Frédéric
F
Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.
Das
Chittaranjan
C
Bowman
Michael J
MJ
Wolfe
Michael S
MS
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
D010455:Peptides; D011480:Protease Inhibitors; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases