主催: 日本薬学会化学系薬学部会
The highly agglutinative feature of Aβ1-42 is a significant obstacle for establishing a reliable in vitro biological experiment system to investigate the major causative agents of Alzheimer's disease (AD) and its related diseases. To solve this problem, based on the O-acyl isopeptide method, we have developed novel pH-triggered "click peptides" of wild- and mutant-type Aβ1-42s, "26-O-acyl isoAβ1-42s (26-AIAβ42s)". These isopeptides suppressed the agglutinative nature of each Aβ1-42 with only one insertion of the isopeptide structure, and could migrate to the corresponding Aβ1-42 quickly via pH-dependent O-N intramolecular acyl migration reaction (by pH-triggered "click"). The method would provide a novel biological evaluation system in AD-related research, in which 26-AIAβ42 can be stored in a solubilized form and rapidly produces intact Aβ1-42 in situ during biological experiments.