Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase

Frédéric Bihel; Chittaranjan Das; Michael J Bowman; Michael S Wolfe

doi:10.1021/jm049788c

Discovery of a Subnanomolar helical D-tridecapeptide inhibitor of gamma-secretase

J Med Chem. 2004 Jul 29;47(16):3931-3. doi: 10.1021/jm049788c.

Authors

Frédéric Bihel¹, Chittaranjan Das, Michael J Bowman, Michael S Wolfe

Affiliation

¹ Center for Neurologic Diseases, Harvard Medical School and Brigham & Women's Hospital, 77 Avenue Louis Pasteur, Boston, Massachusetts 02115, USA.

PMID: 15267231
DOI: 10.1021/jm049788c

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.

Publication types

Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

MeSH terms

Amyloid Precursor Protein Secretases
Circular Dichroism
Endopeptidases / chemistry*
Peptides / chemical synthesis*
Peptides / chemistry
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Protein Structure, Secondary
Stereoisomerism
Structure-Activity Relationship

Substances

Peptides
Protease Inhibitors
Amyloid Precursor Protein Secretases
Endopeptidases