Controlled Production of Amyloid β Peptide from a Photo-Triggered, Water-Soluble Precursor "Click Peptide"

In biological experiments, poor solubility and uncontrolled assembly of amyloid beta peptide (A beta) 1-42 pose significant obstacles to establish an experiment system that clarifies the function of A beta 1-42 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 hod nearly 100-fold higher water solubility than A beta 1-42 and did not self-assemble, as the isomerized structure in its peptide backbone drastically changed the conformation that was derived from A beta 1-42. Moreover, the click peptide afforded A beta 1-42 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 A beta 1-42 from the click peptide could improve the difficulties in handling A beta 1-42 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 beta 1-42 in AD.