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Controlled Production of Amyloid β Peptide from a Photo‐Triggered, Water‐Soluble Precursor “Click Peptide“
Author(s) -
Taniguchi Atsuhiko,
Skwarczynski Mariusz,
Sohma Youhei,
Okada Takuma,
Ikeda Keisuke,
Prakash Halan,
Mukai Hidehito,
Hayashi Yoshio,
Kimura Tooru,
Hirota Shun,
Matsuzaki Katsumi,
Kiso Yoshiaki
Publication year - 2008
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800503
Subject(s) - peptide , click chemistry , chemistry , amyloid (mycology) , peptide synthesis , p3 peptide , biochemistry , biophysics , amyloid precursor protein , combinatorial chemistry , biology , medicine , alzheimer's disease , inorganic chemistry , disease
Abstract In biological experiments, poor solubility and uncontrolled assembly of amyloid β peptide (Aβ) 1–42 pose significant obstacles to establish an experiment system that clarifies the function of Aβ1–42 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 Aβ1–42 and did not self‐assemble, as the isomerized structure in its peptide backbone drastically changed the conformation that was derived from Aβ1–42. Moreover, the click peptide afforded Aβ1–42 quickly under physiological conditions (pH 7.4, 37 °C) by photoirradiation followed by an O –N intramolecular acyl migration. Because the in situ production of intact Aβ1–42 from the click peptide could improve the difficulties in handling Aβ1–42 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 A β 1–42 in AD.