| References |
| Synonyms |
- β-Secretase Inhibitor Screening Assay Kit
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| Stability |
6 months |
| Storage |
-80°C |
| Shipping |
Dry ice
in continental US; may vary elsewhere
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Background Reading
Grüninger-Leitch, F., Schlatter, D., Küng, E., et al. Substrate and inhibitor profile of BACE (β-secretase) and comparison with other mammalian aspartic proteases. J Biol Chem 277(7) 4687-4693 (2002).
Stachel, S.J., Coburn, C.A., Steele, T.G., et al. Structure-based design of potent and selective cell-permeable inhibitors of human b-secretase (BACE-1). J Med Chem 47(26) 6447-6450 (2004).
Mancini, F., Naldi, M., Cavrini, V., et al. Multiwell fluorometric and colorimetric microassays for the evaluation of beta-secretase (BACE-1) inhibitors. Anal Bioanal Chem 388 1175-1183 (2007).
Hong, L., Turner, R.T.I., Koelsch, G., et al. Memapsin 2 (β-secretase) as a therapeutic target. Biochem Soc Trans 30(4) 530-534 (2002).
Pietrak, B.L., Crouthamel, M., Tugusheva, K., et al. Biochemical and cell-based assays for characterization of BACE-1 inhibitors. Anal Biochem 342 144-151 (2005).
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| Size |
Global Purchasing |
| 96 wells |
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Description
Accumulation of the β-amyloid peptide (Aβ) in the brain is implicated as the primary cause of neurodegeneration and progression of Alzheimer’s disease (AD).1 The β-amyloid peptide is derived from sequential proteolytic cleavage of the amyloid precursor protein (APP) by β- and γ-secretases. Initial cleavage by β-secretase (BACE; β-site of APP cleaving enzyme), a membrane anchored aspartic protease, generates a soluble N-terminal fragment and a membrane-associated C-terminal fragment.2 The C-terminal fragment then undergoes proteolysis by γ-secretase to give the Aβ peptide.
BACE has been shown to be the major β-secretase and a promising therapeutic target as this protease initiates the first step in Aβ production.1 Inhibition of BACE activity could potentially block the entire cascade of Alzheimer’s disease pathogenesis. In addition, BACE deficient mice do not generate Aβ peptide. In transgenic murine models of AD driven by Aβ overproduction, BACE deficiency rescued memory deficits and cholinergic dysfunction.3 Additionally, the fact that β-secretase is an aspartic protease has also raised the hope that its therapeutic inhibitor can be as successful as that against HIV protease. Cayman’s BACE Inhibitor Screening Assay Kit provides a convenient method for screening human BACE inhibitors. The assay utilizes a synthetic Swedish mutant APP peptide (EVNLDAEF) that has been linked to a fluorophore (EDANS) at one end and to a quenching agent (Dabcyl) at the other.4 After cleavage by BACE, the product (peptide-EDANS) is brightly fluorescent and can be easily analyzed using a fluorescence plate reader or a fluorometer with excitation wavelengths of 335-345 nm and emission wavelengths of 485-510 nm.
1
Hong, L., Turner, R.T.I., Koelsch, G., et al. Memapsin 2 (β-secretase) as a therapeutic target. Biochem Soc Trans 30(4) 530-534 (2002).
2
Grüninger-Leitch, F., Schlatter, D., Küng, E., et al. Substrate and inhibitor profile of BACE (β-secretase) and comparison with other mammalian aspartic proteases. J Biol Chem 277(7) 4687-4693 (2002).
3
Pietrak, B.L., Crouthamel, M., Tugusheva, K., et al. Biochemical and cell-based assays for characterization of BACE-1 inhibitors. Anal Biochem 342 144-151 (2005).
4
Mancini, F., Naldi, M., Cavrini, V., et al. Multiwell fluorometric and colorimetric microassays for the evaluation of beta-secretase (BACE-1) inhibitors. Anal Bioanal Chem 388 1175-1183 (2007).
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