Modular synthetic strategy for N/C‐terminal protected amyloidogenic peptides

Abstract

N/C‐terminal protected amyloidogenic peptides are valuable biomaterials. Optimization of the protective structures at both termini is, however, synthetically laborious because a linear sequence of solid‐phase peptide synthesis protocol (on‐resin peptide assembly/peptide removal from resin/high‐performance liquid chromatography purification) is required for the peptides each time the protective group is modified. In this study, we demonstrate a modular synthetic strategy for the purpose of rapidly deriving the N/C‐terminal structures of amyloidogenic peptides. The precursor sequences that can be easily synthesized due to a non‐amyloidogenic property were stocked as the synthetic intermediates. Condensation of the intermediates with N/C‐terminal units in a liquid phase followed by high‐performance liquid chromatography purification gave the desired peptides P1–P8. The amyloidogenic peptides that have various N/C‐terminal protective structures were therefore synthesized in a labor‐effective manner. This method is suggested to be useful for synthesizing amyloidogenic peptides possessing divergent protective structures at the N/C‐terminus.