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AssigneeMemorial Sloan Kettering Cancer Center
InventorsChristopher Shelton, Yuan Tian, Yueming Li
Estimating the term…
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 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. This disclosure further identifies small polypeptides based on a subsequence motif of Aβ that are shown herein to be potent inhibitors of the activity of γ-secretase.
A method of assaying the activity of γ-secretase comprising the steps of:
A method of assaying the activity of γ-secretase in a cell comprising the steps of:
A method of screening for an inhibitor of γ-secretase activity comprising the steps of:
A method of screening for an inhibitor of γ-secretase activity in a cell comprising the steps of:
A polypeptide comprising at least a portion of a modified Aβ sequence, wherein at least one of the amino acid residues corresponding to residues 17-21 of Aβ (SEQ ID NO:19) is modified.
A polypeptide comprising amino acid-residues 17-21 of Aβ (SEQ ID NO:19) that is ten amino acid residues or less in length.
A polypeptide comprising a retro-inverso Aβ(17-23) sequence.
Dependencies are inferred from the claim text.