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San Jose, CA, United States, 2006/08/02 - As scientific research explores the role of b-Amyloid in Alzheimer’s Disease, the secretases whose cleavage activity produces b-Amyloid fragments have become an important focus..
Amyloid Precursor Protein, APP, a transmembrane glycoprotein of about 770 amino acids, is cleaved by a-Secretase and b-Secretase to produce C-terminal fragments that are 83 amino acids (C83) and 99-amino acids (C99) in length, respectively. Subsequent cleavages of C83 and C99 by g-Secretase produce a 3-kD (p3) protein in the former and a 4-kD (b-amyloid) protein in the latter and a CT57-59 in both fragments (reviewed in 1, 2). The 4-Kd consists of Ab which are 39 to 42 amino acids in length, with Ab 1-42 being the major component of amyloid plaques which accumulates in neurons of Alzheimer’s disease (AD) brain. Consequently, b-Secretase is an important target for AD drug development.
FRET Secretase Substrates
AnaSpec provides fluorescence resonance energy transfer (FRET) substrates for use in measuring b-Secretase activity. Upon cleavage of the FRET substrate by b-Secretase, the quenched fluorescence of the donor is released, with the fluorescence signal increasing with b-Secretase activity. Variations include a range of sequence lengths and emission wavelengths.
· Swedish Double Mutation (K670N/M671L)
EnzoLyte™ 520 ß-Secretase Assay Kit
· Ready-to-use assay kit for detection of b-Secretase V. 100 assays.
b -Secretase inhibitors
· High-purity peptides that inhibit b-Secretase activity.
a -Secretase Substrate
· A FRET-based a-Secretase substrate, which upon cleavage liberates the Mca (7-Methoxycoumarin-4-acetic acid) fragment from the proximity quenching effect of Dnp (2,4-dinitrophenyl), Abs/Em=325/393 nm.
1. Selkoe DJ. Nature 399, A23 (1999).
2. Suh, Y-H. and F. Checler. Pharma. Rev. 54, 469 (2002).
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