presented herein are polypeptide substrates based on notch polypeptides , assay methods based on the use of these substrates , and screening methods directed toward identifying inhibitors of γ - 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 .