Gamma secretase substrates and in vitro assays

C - Chemistry – Metallurgy – 12 – Q

Patent

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Details

C12Q 1/00 (2006.01) A61K 38/00 (2006.01) C07H 21/04 (2006.01) C07K 14/00 (2006.01) C07K 14/47 (2006.01) C12N 9/48 (2006.01) C12Q 1/37 (2006.01) G01N 33/53 (2006.01)

Patent

CA 2408003

The present invention features .gamma.-secretase substrates andin vitro assays for measuring .gamma.-secretase activity employing such substrates. The .gamma.-secretase substrates described herein contain a hydrophilic polypeptide moiety covalently joined to the carboxyl terminus of a .beta.-CTF domain. A ".beta.-CTF domain" is a polypeptide that can be cleaved by .gamma.- secretase and which approximates the C-terminal fragment (amino acids 596-695) of APP produced after cleavage of APP by a .beta.-secretase, or is a functional derivative thereof.

Cette invention se rapporte à des substrats de .gamma.-sécrétase et à des dosages in vitro servant à mesurer l'activité de .gamma.-sécrétase en utilisant de tels substrats. Les substrats de .gamma.-sécrétase décrits ici contiennent une fraction de polypeptide hydrophile jointe par covalence à la terminaison carboxyle d'un domaine .beta.-CTF. Un tel domaine .beta.-CTF est constitué par un polypeptide pouvant être clivé par .gamma.-sécrétase et qui avoisine le fragment terminal C (acides aminés 596-695) d'APP produit après clivage de l'APP par une .beta.-sécrétase ou alors il est constitué par un dérivé fonctionnel de ce polypeptide.

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