Chemistry: molecular biology and microbiology – Enzyme – proenzyme; compositions thereof; process for... – Hydrolase
Patent
1995-06-07
1998-04-28
Lankford, Blaine
Chemistry: molecular biology and microbiology
Enzyme , proenzyme; compositions thereof; process for...
Hydrolase
435219, 435212, C12N 964, C12N 950, C12N 648
Patent
active
057443467
ABSTRACT:
Compositions comprising a novel protease capable of cleaving .beta.-amyloid precursor protein on the amino-terminal side of the .beta.-amyloid peptide therein are provided. The protease is designated .beta.-secretase. The .beta.-secretase may be used in screening assays to identify .beta.-secretase inhibitors, or the .beta.-secretase is combined with a suitable polypeptide substrate and cleavage of the substrate determined in the presence and absence of the test substance.
REFERENCES:
Genevieve, E. et al. "Alzheimer's disease amyloid precursor protein (A.beta.pp): proteolytic processing, secretases and .beta.A4 amyloid production," (1994) Amyloid: Int. J. Exp. Clin. Invest., 1, 263-280.
Matsumoto, A. et al. "Ca.sup.2+ -Dependent 68-Kilodalton Protease in Familial Alzheimer's Disease Cells Cleaves the n-Terminus of .beta.-Amyloid," (1994) Biochemistry, 33, 3941-3948.
Citron, M. et al. "Generation of Amyloid .beta. Protein from Its Precursor is Sequence Specific," (1995) Neuron, 14, 661-670.
Matsumoto, A. et al. "Molecular cloning of human cDNA with a sequence highly similar to that of the dihydrofolate reductase gene in brain libraries derived from Alzheimer's disease patients," (1995) Eur. J. Biochem. 230, 337-343.
Brown, A. et al. "Evaluation of cathepsins d and G and EC 3.4.24.15 as Candidate .beta.-Secretase Proteases Using Peptide and Amyloid Precursor Protein Substrates," (1996) J. Neurochem. vol. 66, No. 6, pp. 2436-2445.
Kang, Jie et al. "The precursor of Alzheimer's disease amyloid A4 protein resembles a cell-surface receptor," (1987) Nature vol. 325 pp. 733-736.
HAASS, Christian et al. "Amyloid .beta.-peptide is produced by cultured cells during normal metabolism," (1992) Nature vol. 359 pp. 322-325.
Seubert, Paul et al. "Isolation and quanticication of soluble Alzheimer's .beta.-peptide from biological fluids," (1992) Nature vol. 359 pp. 325-327.
Selkoe, Dennis J. "Cell Biology of the Amyloid .beta.-Protein Precursor and the Mechanism of Alzheimer's Disease," (1994) Annu. Rev. Cell Biol. pp. 373-403.
Anderson John P.
Chrysler Susanna M. S.
Keim Pamela S.
Sinha Sukanto
Athena Neurosciences, Inc.
Lankford Blaine
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