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

Abstract

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.

• Authors: Atsuhiko Taniguchi, Youhei Sohma, Maiko Kimura, Takuma Okada, Keisuke Ikeda, Yoshio Hayashi, Tooru Kimura, Shun Hirota, Katsumi Matsuzaki, Yoshiaki Kiso
• Journal: Journal of the American Chemical Society (J Am Chem Soc) Vol. 128 Issue 3 Pg. 696-7 (Jan 25 2006) ISSN: 0002-7863 [Print] United States
• PMID: 16417340 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Peptide Fragments
• amyloid beta-protein (1-42)

Topics

• Alzheimer Disease (metabolism)
• Amino Acid Sequence
• Amyloid beta-Peptides (chemistry, metabolism)
• Hydrogen-Ion Concentration
• Molecular Sequence Data
• Peptide Fragments (chemistry, metabolism)
• Photochemistry
• Spectrophotometry, Ultraviolet