Understanding of the dynamic events of Aβ1-42, such as the folding, self-assembly, and aggregation processes, is of great significance in Alzheimer' s disease (AD) research. Based on the O-acyl isopeptide method, we have developed a novel "click peptide" of Aβ1-42, "26-O-acyl isoAβ1-42 (26-AIA-42)". This click peptide suppresses the agglutinative nature of Aβ1-42 with only one insertion of an isopeptide structure during SPPS, and could migrate to the original Aβ1-42 quickly via a pH-dependent O-N intramolecular acyl migration reaction (by pH-triggered "click"). In addition, we have synthesized a photo-triggered "click peptide" of Aβ1-42, i.e., 26-N-Nvoc-26-O-acyl isoAβ1-42 to provide a novel biological evaluation system with high spatial and temporal resolution in AD-related research.
