Synthesis of amyloid beta peptide 1-42 (E22Delta) click peptide: pH-triggered in situ production of its native form.
Amyloid beta peptide (Abeta) 1-42 is known to be involved in the onset of Alzheimer's disease (AD). We developed a click peptide of Abeta1-42 as a useful tool for AD research on the basis of an O-acyl isopeptide method. The click peptide quickly produced intact Abeta1-42 via a pH-dependent O-to-N intramolecular acyl migration (pH-click). Herein, a click peptide (26-O-acyl isoAbeta1-42 (E22Delta)) of a new mutant Abeta1-42 (E22Delta) was synthesized. The mutant click peptide was more water-soluble than Abeta1-42 (E22Delta). Moreover it quantitatively converted to the native peptide under physiological conditions (pH 7.4, 37 degrees C). CD analyses showed a conformational change from a random-coil structure of the click peptide to a beta-sheet structure of the in situ produced Abeta1-42 (E22Delta). This click peptide is a useful precursor of a mutant Abeta1-42 to establish an experiment system for investigating the properties of the mutant.
Wang
Hui
H
Department of Medicinal Chemistry, Center for Frontier Research in Medicinal Science, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto 607-8412, Japan.
Kakizawa
Taeko
T
Taniguchi
Atsuhiko
A
Mizuguchi
Takaaki
T
Kimura
Tooru
T
Kiso
Yoshiaki
Y
D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000235:genetics*; D002942:Circular Dichroism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008969:Molecular Sequence Data; D009154:Mutation; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D012995:Solubility; D014867:Water / Q000737:chemistry
D016229:Amyloid beta-Peptides; C544092:beta-amyloid peptide 1-42 (E22delta) click peptide; D014867:Water