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“Click Peptide“: pH‐Triggered in Situ Production and Aggregation of Monomer Aβ1–42
Author(s) -
Taniguchi Atsuhiko,
Sohma Youhei,
Hirayama Yuta,
Mukai Hidehito,
Kimura Tooru,
Hayashi Yoshio,
Matsuzaki Katsumi,
Kiso Yoshiaki
Publication year - 2009
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.200800765
Subject(s) - peptide , monomer , random coil , chemistry , click chemistry , fibril , peptide synthesis , sequence (biology) , intramolecular force , biophysics , peptide sequence , in situ , combinatorial chemistry , circular dichroism , stereochemistry , biochemistry , organic chemistry , biology , polymer , gene
Into neutral : We demonstrate the unique features of a pH click peptide based on an O‐acyl isopeptide method. Under acidic conditions, the click peptide remains in a monomeric form. Upon increase of the pH to 7.4, the click peptide is quickly able to convert into Aβ1–42 through an O‐to‐N intramolecular acyl migration. Further study using this pH click peptide would elucidate the pathological role of Aβ1–42 in Alzheimer's disease.The intense and uncontrollable self‐assembling nature of amyloid β peptide (A β ) 1–42 is known to cause difficulties in preparing monomeric A β 1–42; this results in irreproducible or discrepant study outcomes. Herein, we report novel features of a pH click peptide of A β 1–42 that was designed to overcome these problems. The click peptide is a water‐soluble precursor peptide of A β 1–42 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 Aβ1–42 promptly ( t 1/2 ≈10 s) and quantitatively through an O‐to‐N intramolecular acyl migration. As a result of this quick and irreversible conversion, monomer Aβ1–42 with a random coil structure is produced in situ. Moreover, the oligomerization, amyloid fibril formation and conformational changes of the produced Aβ1–42 can be observed over time. This click peptide strategy should provide a reliable experimental system to investigate the pathological role of Aβ1–42 in Alzheimer's disease.