Stable β-sheet formation and enhanced hydrolytic catalysis of a sequential alternating amphiphilic polypeptide containing catalytic triads in a serine protease

Article abstract of DOI:10.1246/bcsj.69.431

The alternating amphiphilic copolypeptide poly(Asp-Leu-His-Leu-Ser-Leu) was prepared by the synthesis and polymerization of the respective hexapeptide in order to obtain a stable β-sheet polypeptide with hydrolytic catalytic activity, like that of a serine protease. The conformation and conformational transitions in aqueous solution and in water-organic solvent mixtures were determined by circular dichroism measurements. The polypeptide reveals a very strong tendency to adopt a β-sheet structure, which is accomplished at below pH 10.0, and even by adding sodium chloride or various alcohols. However, a partial α-helical conformation is observed in an aqueous solution at pH 12.0; also, an α-helix to β-sheet conformational transition occurs upon adding 1 M NaCl. The polypeptide is a more effective catalyst than the peptide hexamer, the amino acids mixture, or imidazole for the hydrolysis of p-nitrophenyl derivatives, and catalyzed the hydrolytic reaction of the substrates more effectively with increasing their hydrophobicity. It is likely that the enhanced hydrolytic catalyst of the polypeptide may be responsible for increasing the nucleophilicity by the electrostatic interactions or condensation effect of the substrates by hydrophobic interactions. The polypeptide would make good models for constructing novel proteins with catalytic properties involving β-sheet structures.