Patent ID: 7803739

Claim:
A method for assaying for modulators of β-secretase activity, comprising: (a) contacting a polypeptide with β-secretase APP processing activity with a substrate, both in the presence and in the absence of a putative modulator compound; wherein said substrate comprises a peptide having an amino acid sequence of at least 6 amino acids, said amino acid sequence including four amino acids defined by formula P 2 P 1 -P 1′ P 2′ , wherein: P 2 is N; P 1 comprises an amino acid selected from the group consisting of Y, L, and F; P 1′ , comprises an amino acid selected from the group consisting of E, A, and D; P 2′ , is V; wherein the substrate is cleaved between P 1 and P 1′ by a human aspartyl protease encoded by the nucleic acid sequence of SEQ ID NO: 1 or SEQ ID NO: 3 (Hu-Asp2); and wherein said peptide does not comprise the corresponding P 2 P 1 -P 1′ P 2′ portion of amino acid sequence depicted in SEQ ID NO: 34; (b) measuring cleavage of the substrate peptide in the presence and in the absence of the putative modulator compound; and (c) identifying modulators of β-secretase activity from a difference in substrate cleavage in the presence versus in the absence of the putative modulator compound, wherein a modulator that is a β-secretase antagonist reduces such cleavage and a modulator that is a β-secretase agonist increases such cleavage.