Elizabeth M Dodson

US Patent:

20030200555, Oct 23, 2003

Filed:

Apr 30, 2003

Appl. No.:

10/427208

Inventors:

Daria Hazuda - Doylestown PA, US
Elizabeth Dodson - Souderton PA, US
Min Xu - Ambler PA, US
Xiao-Ping Shi - Warrington PA, US
Adam Simon - Langborne PA, US
Guoxin Wu - Merion Station PA, US
Yueming Li - New York NY, US
Robert Register - Evergreen CO, US

International Classification:

A01K067/027
A61K031/00
G01N033/53
G01N033/567
C07H021/04
A61K039/395
C12N009/64

US Classification:

800/012000, 800/018000, 435/226000, 424/146100, 530/388260, 514/001000, 435/007200, 435/354000, 435/320100, 536/023200

Abstract:

Provided are methods of identifying inhibitors of -secretase that employ modified -secretase substrates. The modified -secretase substrates have -secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered -secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1′-P2′ of the -secretase cleavage site. Many of the modified -secretase substrates are more efficient substrates for -secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by -secretase. Recombinant polynucleotide molecules encoding the modified -secretase substrates are provided. Antibodies that recognize cleavage products of the modified -secretase substrates are provided. Stable cell lines expressing the modified -secretase substrates are provided. Transgenic animals expressing the modified -secretase substrates are provided.

US Patent:

20070219354, Sep 20, 2007

Filed:

Mar 7, 2007

Appl. No.:

11/714985

Inventors:

Daria Hazuda - Doylestown PA, US
Elizabeth Chen Dodson - Souderton PA, US
Min Xu - Ambler PA, US
Xiao-Ping Shi - Warrington PA, US
Adam Simon - Langhorne PA, US
Guoxin Wu - Merion Station PA, US
Yueming Li - New york NY, US
Bruce Register - Berwyn PA, US

International Classification:

C07K 16/00
C07K 14/00

US Classification:

530387900, 530395000

Abstract:

Provided are methods of identifying inhibitors of β-secretase that employ modified β-secretase substrates. The modified β-secretase substrates have β-secretase cleavage sites that are altered from wild type. The amino acid sequences of the altered β-secretase cleavage sites contain different amino acids in at least one of the positions P2-P1-P1′-P2′ of the β-secretase cleavage site. Many of the modified β-secretase substrates are more efficient substrates for β-secretase than are corresponding substrates having wild-type sequences, that is, these modified substrates are more susceptible to enzymatic breakdown by β-secretase. Recombinant polynucleotide molecules encoding the modified β-secretase substrates are provided. Antibodies that recognize cleavage products of the modified β-secretase substrates are provided. Stable cell lines expressing the modified β-secretase substrates are provided. Transgenic animals expressing the modified β-secretase substrates are provided.