Amyloid beta peptide (Aβ)-related studies require an adequate supply of purified Aβ peptide. However, Aβ peptides are “difficult sequences” to synthesize chemically, and low yields are common due to aggregation during purification. Here, we demonstrate an easier synthesis, deprotection, reduction, cleavage, and purification process for Aβ(1-40) using standard 9-fluorenylmethyloxycarbonyl (Fmoc)-protected amino acids and solid-phase peptide synthesis (SPPS) resin [HMBA (4-hydroxymethyl benzamide) resin] that provides higher yields of Aβ(1-40) than previous standard protocols. Furthermore, purification requires a similar amount of time as conventional purification processes, although the peptide must be cleaved from the resin immediately prior to purification. The method described herein is not limited to the production of Aβ(1-40), and can be used to synthesize other easily-oxidized and aggregating sequences. Our proposed methodology will contribute to various fields using “difficult sequence” peptides, such as pharmaceutical and materials science, as well as research for the diagnosis and treatment of protein/peptide misfolding diseases.
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