Abstract: Polypeptide substrates based on modifications or fragments of the various APP isoforms, assay methods based on the use of these substrates, and screening methods directed toward identifying inhibitors of ?-secretase activity. The assay methods and the screening methods are adapted for use in high throughput multi-well plate assay apparatuses. In many embodiments the substrate polypeptides are labeled for ease of detection, and/or may bind specific ligands that themselves are labeled. Generally the labels promote high specificity as well as high sensitivity of detection. These features render the assay and screening methods that employ the labeled substrates especially suited for use in high throughput assay formats. This disclosure further identifies small polypeptides based on a subsequence motif of A? that are shown herein to be potent inhibitors of the activity of ?-secretase.

Abstract: Compounds including those of the Formula I where X, R1, R2 and subscript t are as defined herein, useful as ?-secretase inhibitors, are provided, as are compositions comprising the compounds, as well as methods for use of the compounds for treating or preventing neurodegenerative diseases, such as, for instance, Alzheimer's disease.

Abstract: Polypeptide substrates based on modifications or fragments of the various APP isoforms, assay methods based on the use of these substrates, and screening methods directed toward identifying inhibitors of ?-secretase activity. The assay methods and the screening methods are adapted for use in high throughput multi-well plate assay apparatuses. In many embodiments the substrate polypeptides are labeled for ease of detection, and/or may bind specific ligands that themselves are labeled. Generally the labels promote high specificity as well as high sensitivity of detection. These features render the assay and screening methods that employ the labeled substrates especially suited for use in high throughput assay formats. This disclosure further identifies small polypeptides based on a subsequence motif of A? that are shown herein to be potent inhibitors of the activity of ?-secretase.

Abstract: Compounds including those of the Formula I where X, R1, R2 and subscript t are as defined herein, useful as ?-secretase inhibitors, are provided, as are compositions comprising the compounds, as well as methods for use of the compounds for treating or preventing neurodegenerative diseases, such as, for instance, Alzheimer's disease.

Abstract: Polypeptide substrates based on modifications or fragments of the various APP isoforms, assay methods based on the use of these substrates, and screening methods directed toward identifying inhibitors of ?-secretase activity. The assay methods and the screening methods are adapted for use in high throughput multi-well plate assay apparatuses. In many embodiments the substrate polypeptides are labeled for ease of detection, and/or may bind specific ligands that themselves are labeled. Generally the labels promote high specificity as well as high sensitivity of detection. These features render the assay and screening methods that employ the labeled substrates especially suited for use in high throughput assay formats. This disclosure further identifies small polypeptides based on a subsequence motif of A? that are shown herein to be potent inhibitors of the activity of ?-secretase.