Synthesis of amyloid β peptide 1–42 (E22Δ) click peptide: pH-triggered in situ production of its native form

Abstract Amyloid β peptide (Aβ) 1–42 is known to be involved in the onset of Alzheimer’s disease (AD). We developed a click peptide of Aβ1–42 as a useful tool for AD research on the basis of an O -acyl isopeptide method. The click peptide quickly produced intact Aβ1–42 via a pH-dependent O -to- N intramolecular acyl migration (pH-click). Herein, a click peptide (26- O -acyl isoAβ1–42 (E22Δ)) of a new mutant Aβ1–42 (E22Δ) was synthesized. The mutant click peptide was more water-soluble than Aβ1–42 (E22Δ). Moreover it quantitatively converted to the native peptide under physiological conditions (pH 7.4, 37 °C). CD analyses showed a conformational change from a random-coil structure of the click peptide to a β-sheet structure of the in situ produced Aβ1–42 (E22Δ). This click peptide is a useful precursor of a mutant Aβ1–42 to establish an experiment system for investigating the properties of the mutant.