title: "Click peptide": pH-triggered in situ production and aggregation of monomer Abeta1-42.
abstract: The intense and uncontrollable self-assembling nature of amyloid beta peptide (Abeta) 1-42 is known to cause difficulties in preparing monomeric Abeta1-42; this results in irreproducible or discrepant study outcomes. Herein, we report novel features of a pH click peptide of Abeta1-42 that was designed to overcome these problems. The click peptide is a water-soluble precursor peptide of Abeta1-42 with an O-acyl isopeptide structure between the Gly25-Ser26 sequence. The click peptide adopts and retains a monomeric, random coil state under acidic conditions. Upon change to neutral pH (pH click), the click peptide converts to Abeta1-42 promptly (t(1/2) approximately 10 s) and quantitatively through an O-to-N intramolecular acyl migration. As a result of this quick and irreversible conversion, monomer Abeta1-42 with a random coil structure is produced in situ. Moreover, the oligomerization, amyloid fibril formation and conformational changes of the produced Abeta1-42 can be observed over time. This click peptide strategy should provide a reliable experimental system to investigate the pathological role of Abeta1-42 in Alzheimer's disease.
authors.affiliation: Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, 21st Century COE Program, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, Japan. kiso@mb.kyoto-phu.ac.jp
authors.forename: Atsuhiko
authors.initials: A
authors.lastname: Taniguchi
authors.forename: Youhei
authors.initials: Y
authors.lastname: Sohma
authors.forename: Yuta
authors.initials: Y
authors.lastname: Hirayama
authors.forename: Hidehito
authors.initials: H
authors.lastname: Mukai
authors.forename: Tooru
authors.initials: T
authors.lastname: Kimura
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Hayashi
authors.forename: Katsumi
authors.initials: K
authors.lastname: Matsuzaki
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Kiso
mesh_terms: D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism*; D011485:Protein Binding; D011487:Protein Conformation; D011498:Protein Precursors / Q000737:chemistry / Q000378:metabolism*; D055550:Protein Stability; D013997:Time Factors
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D011498:Protein Precursors; C075222:amyloid beta-protein (1-42)