Gamma secretase substrates and in vitro assays
OwnerYueming Li, Min Xu +2inventors
InventorsYueming Li, Min Xu, Qian Huang, Stephen J Gardell
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Abstract
The present invention features γ-secretase substrates and in vitro assays for measuring γ-secretase activity employing such substrates. The γ-secretase substrates described herein contain a hydrophilic polypeptide moiety covalently joined to the carboxyl terminus of a β-CTF domain. A “β-CTF domain” is a polypeptide that can be cleaved by γ-secretase and which approximates the C-terminal fragment (amino acids 596-695) of APP produced after cleavage of APP by a β-secretase, or is a functional derivative thereof.
Claims19
A γ-secretase substrate consisting of:
- a) a β-CTF domain;
- and
- b) a hydrophilic polypeptide moiety covalently joined to the carboxyl terminus of said β-CTF domain.
A method for assaying γ-secretase activity comprising the step of measuring cleavage of the substrate of any one of clams 1-9 by γ-secretase in the presence of an effective amount of a zwitterionic detergent.
A method for measuring the ability of a compound to affect γ-secretase activity comprising the steps of:
- a) combining together the substrate of any one of clams 1-9, said compound, and a preparation comprising γ-secretase activity, under reaction conditions allowing for γ-secretase activity, wherein said reaction conditions comprise an effective amount of a zwitterionic detergent;
- and
- b) measuring γ-secretase activity.
Dependencies are inferred from the claim text.