title: 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.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Kyoto, Japan.
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Taniguchi
authors.forename: Mariusz
authors.initials: M
authors.lastname: Skwarczynski
authors.forename: Youhei
authors.initials: Y
authors.lastname: Sohma
authors.forename: Takuma
authors.initials: T
authors.lastname: Okada
authors.forename: Keisuke
authors.initials: K
authors.lastname: Ikeda
authors.forename: Halan
authors.initials: H
authors.lastname: Prakash
authors.forename: Hidehito
authors.initials: H
authors.lastname: Mukai
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Tooru
authors.initials: T
authors.lastname: Kimura
authors.forename: Shun
authors.initials: S
authors.lastname: Hirota
authors.forename: Katsumi
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry* / Q000378:metabolism; D040761:Biomimetic Materials / Q000737:chemistry; D002942:Circular Dichroism; D008956:Models, Chemical; D008969:Molecular Sequence Data; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000528:radiation effects*; D010777:Photochemistry; D011487:Protein Conformation / Q000528:radiation effects; D012995:Solubility
chemical_list: D016229:Amyloid beta-Peptides; D010455:Peptides