Controlled production of amyloid beta peptide from a photo-triggered, water-soluble precursor "click peptide".

Abstract

In biological experiments, poor solubility and uncontrolled assembly of amyloid beta peptide (Abeta) 1-42 pose significant obstacles to establish an experiment system that clarifies the function of Abeta1-42 in Alzheimer's disease (AD). Herein, as an experimental tool to overcome these problems, we developed a water-soluble photo-"click peptide" with a coumarin-derived photocleavable protective group that is based on an O-acyl isopeptide method. The click peptide had nearly 100-fold higher water solubility than Abeta1-42 and did not self-assemble, as the isomerized structure in its peptide backbone drastically changed the conformation that was derived from Abeta1-42. Moreover, the click peptide afforded Abeta1-42 quickly under physiological conditions (pH 7.4, 37 degrees C) by photoirradiation followed by an O-N intramolecular acyl migration. Because the in situ production of intact Abeta1-42 from the click peptide could improve the difficulties in handling Abeta1-42 caused by its poor solubility and highly aggregative nature, this click peptide strategy would provide a reliable experiment system for investigating the pathological function of Abeta1-42 in AD.

• Authors: Atsuhiko Taniguchi, Mariusz Skwarczynski, Youhei Sohma, Takuma Okada, Keisuke Ikeda, Halan Prakash, Hidehito Mukai, Yoshio Hayashi, Tooru Kimura, Shun Hirota, Katsumi Matsuzaki, Yoshiaki Kiso
• Journal: Chembiochem : a European journal of chemical biology (Chembiochem) Vol. 9 Issue 18 Pg. 3055-65 (Dec 15 2008) ISSN: 1439-7633 [Electronic] Germany
• PMID: 19025862 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amyloid beta-Peptides
• Peptides

Topics

• Amino Acid Sequence
• Amyloid beta-Peptides (chemistry, metabolism)
• Biomimetic Materials (chemistry)
• Circular Dichroism
• Models, Chemical
• Molecular Sequence Data
• Peptides (chemical synthesis, chemistry, radiation effects)
• Photochemistry
• Protein Conformation (radiation effects)
• Solubility