公开(公告)号：US20070292895A1

公开(公告)日：2007-12-20

申请号：US11803207

申请日：2007-05-14

申请人： Xiao-Ping Shi ,  Guoxin Wu ,  Jason Kahana ,  Adam Simon

发明人： Xiao-Ping Shi ,  Guoxin Wu ,  Jason Kahana ,  Adam Simon

IPC分类号： G01N33/573

CPC分类号： G01N33/6896 ,  G01N2333/948 ,  G01N2800/2821 ,  G01N2800/52

摘要： Methods and assays for detecting β-secretase (BACE-1) activity in body fluids or tissue extracts from individuals, particularly individuals who have Alzheimer's disease, are disclosed. A truncated form of BACE-1 was isolated that can be used as a biomarker for Alzheimer's disease.

摘要翻译： 公开了用于检测来自个体，特别是患有阿尔茨海默病的个体的体液或组织提取物中的β-分泌酶（BACE-1）活性的方法和测定法。 分离出截短形式的BACE-1，其可用作阿尔茨海默病的生物标志物。

公开(公告)号：US20070219354A1

公开(公告)日：2007-09-20

申请号：US11714985

申请日：2007-03-07

申请人： Daria Hazuda ,  Elizabeth Chen Dodson ,  Ming-Tain Lai ,  Min Xu ,  Xiao-Ping Shi ,  Adam Simon ,  Guoxin Wu ,  Yueming Li ,  Bruce Register

发明人： Daria Hazuda ,  Elizabeth Chen Dodson ,  Ming-Tain Lai ,  Min Xu ,  Xiao-Ping Shi ,  Adam Simon ,  Guoxin Wu ,  Yueming Li ,  Bruce Register

IPC分类号： C07K16/00 ,  C07K14/00

CPC分类号： C07K7/06 ,  A01K2217/05 ,  A01K2267/0306 ,  A61K38/00 ,  C07K5/1016 ,  C07K5/1019 ,  C07K5/1021 ,  C07K14/4711 ,  C07K16/18 ,  C12P21/06 ,  C12Q1/37 ,  G01N33/5088 ,  G01N33/6896 ,  G01N2500/00 ,  G01N2800/52

摘要： 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.

公开(公告)号：US07196163B2

公开(公告)日：2007-03-27

申请号：US10427208

申请日：2003-04-30

申请人： Daria Jean Hazuda ,  Elizabeth Chen Dodson ,  Ming-Tain Lai ,  Min Xu ,  Xiao-Ping Shi ,  Adam J. Simon ,  Guoxin Wu ,  Yueming Li ,  Bruce Register

发明人： Daria Jean Hazuda ,  Elizabeth Chen Dodson ,  Ming-Tain Lai ,  Min Xu ,  Xiao-Ping Shi ,  Adam J. Simon ,  Guoxin Wu ,  Yueming Li ,  Bruce Register

IPC分类号： A61K38/07 ,  A61K38/16

CPC分类号： C07K7/06 ,  A01K2217/05 ,  A01K2267/0306 ,  A61K38/00 ,  C07K5/1016 ,  C07K5/1019 ,  C07K5/1021 ,  C07K14/4711 ,  C07K16/18 ,  C12P21/06 ,  C12Q1/37 ,  G01N33/5088 ,  G01N33/6896 ,  G01N2500/00 ,  G01N2800/52

摘要： 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.

摘要翻译： 提供了鉴定使用修饰的β-分泌酶底物的β-分泌酶抑制剂的方法。 修饰的β-分泌酶底物具有从野生型改变的β-分泌酶切割位点。 改变的β-分泌酶切割位点的氨基酸序列在β-分泌酶切割位点的至少一个位置P2-P1-P1'-P2'中含有不同的氨基酸。 许多修饰的β-分泌酶底物比具有野生型序列的相应底物更有效的β-分泌酶底物，也就是说，这些修饰的底物更易受β-分泌酶的酶分解。 提供了编码经修饰的β-分泌酶底物的重组多核苷酸分子。 提供了识别修饰的β-分泌酶底物的切割产物的抗体。 提供了表达改良的β-分泌酶底物的稳定细胞系。 提供了表达改良的β-分泌酶底物的转基因动物。