title: Amplified voltammetric characterization of cleavage of the biotinylated peptide by BACE1 and screening of BACE1 inhibitors.
abstract: Cleavage of amyloid precursor protein (APP) by the β-site APP cleaving enzyme 1 (BACE1) is a key step in the formation of amyloid beta (Aβ) peptide, the main component of amyloid plaques in Alzheimer's disease (AD). Suppression of BACE1 activity has thus become an efficient way for the treatment of AD. In this study, BACE1 in the absence or presence of BACE1 inhibitors was exposed to the biotinylated peptide substrate-modified electrode. This step was followed by the attachment of ferrocene (Fc)-capped gold nanoparticle/streptavidin conjugates. Due to the blockage of the BACE1 activity by select inhibitors, well-defined voltammetric peaks of high signal intensity were obtained. However, featureless voltammogram was obtained upon initiating the cleavage reaction. The proposed method is simple, sensitive, and suitable for monitoring of BACE1 activity and screening of BACE1 inhibitors.
authors.affiliation: College of Chemistry and Chemical Engineering, Central South University, Changsha, Hunan 410083, People's Republic of China.
authors.forename: Xinyao
authors.initials: X
authors.lastname: Yi
authors.forename: Hongxing
authors.initials: H
authors.lastname: Han
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jianxiu
authors.initials: J
authors.lastname: Wang
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhang
authors.forename: Feimeng
authors.initials: F
authors.lastname: Zhou
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology; D000595:Amino Acid Sequence; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D015374:Biosensing Techniques; D019921:Biotinylation; D004353:Drug Evaluation, Preclinical; D055664:Electrochemical Techniques; D057075:Enzyme Assays; D006046:Gold / Q000737:chemistry; D006801:Humans; D008969:Molecular Sequence Data; D053758:Nanoparticles / Q000737:chemistry; D010455:Peptides / Q000737:chemistry / Q000378:metabolism*
chemical_list: D010455:Peptides; D006046:Gold; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human
keywords: BACE1 activity; BACE1 inhibitor; Biotinylated peptide substrate; Fc-capped gold nanoparticle/streptavidin conjugates; Voltammetry