"Click peptide" based on the "o-acyl isopeptide method": control of A beta1-42 production from a photo-triggered A beta1-42 analogue

A clear understanding of the dynamic events of amyloid beta peptide (Abeta) 1-42, such as the folding, self-assembly, and aggregation processes, would be of great significance in Alzheimer's disease (AD) research. However, elucidation of these Abeta1-42 dynamic events is a difficult issue due t...

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Bibliographic Details
Published in:Journal of the American Chemical Society 2006-01, Vol.128 (3), p.696-697
Main Authors: Taniguchi, Atsuhiko, Sohma, Youhei, Kimura, Maiko, Okada, Takuma, Ikeda, Keisuke, Hayashi, Yoshio, Kimura, Tooru, Hirota, Shun, Matsuzaki, Katsumi, Kiso, Yoshiaki
Format: Article
Language:English
Subjects:
Alzheimer Disease - metabolism
Amino Acid Sequence
Amyloid beta-Peptides - chemistry
Amyloid beta-Peptides - metabolism
Hydrogen-Ion Concentration
Molecular Sequence Data
Peptide Fragments - chemistry
Peptide Fragments - metabolism
Photochemistry
Spectrophotometry, Ultraviolet
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Summary:A clear understanding of the dynamic events of amyloid beta peptide (Abeta) 1-42, such as the folding, self-assembly, and aggregation processes, would be of great significance in Alzheimer's disease (AD) research. However, elucidation of these Abeta1-42 dynamic events is a difficult issue due to uncontrolled polymerization, which also poses a significant obstacle for establishing an experimental system that clarifies the pathological function of Abeta1-42. On the basis of the O-acyl isopeptide method, we herein developed a novel photo-triggered "click peptide" of Abeta1-42, for example, 26-N-Nvoc-26-AIAbeta42, in which the photocleavable 6-nitroveratryloxycarbonyl (Nvoc) group was introduced at the alpha-amino group of Ser26 in 26-O-acyl isoAbeta1-42 (26-AIAbeta42). From the results, (1) the click peptide did not exhibit the self-assembling nature under physiological conditions due to one single modified ester; (2) photoirradiation of the click peptide and subsequent O-N intramolecular acyl migration afforded the intact Abeta1-42 with a quick and one-way conversion reaction (so-called "click"), while the click peptide was stable under nonphotolytic or storage conditions. In addition, it is advantageous that no additional fibril inhibitory auxiliaries were released during conversion to Abeta1-42. This method provides a novel system useful for investigating the dynamic biological functions of Abeta1-42 in AD by inducible activation of Abeta1-42 self-assembly.
ISSN:0002-7863