Maiko Kimura

The “O-Acyl Isopeptide Method” for the Synthesis of Alzheimer’s Disease-Related Amyloid β Peptide (Aβ) 1–42

Introduction Many studies using synthetic Aβ1–42 have been carried out to clarify the involvement of Aβ1–42 in Alzheimer’s disease (AD). However, the pathological self-assembly of Aβ1–42 in amyloid plaque formation, a currently unexplained process, is very difficult to demonstrate in vitro due to its uncontrolled polymerization. For example, synthesized Aβ1–42 already contains variable oligomeric forms [1], as Aβ1–42 undergoes aggregation in an aqueous TFA– acetonitrile solution used in HPLC purification. Additionally, the Aβ1–42 monomer easily forms an aggregate even in a standard storage solution such as dimethylsulfoxide (DMSO) [2]. The highly agglutinative property of Aβ1–42 also results in synthetic difficulties with this peptide, a so-called “difficult sequencecontaining peptide” [3]. To solve these problems, based on the “O-acyl isopeptide method” [4], we have developed a novel water-soluble isopeptide of wild-type Aβ1–42, “26-O-acyl isoAβ1–42 (26-AIAβ42)” (Fig. 1) [5].