Insufficient solubility, fragile folding structure and short half-life frequently hamper use of peptides as biological reagents or therapies. To enhance the peptide function, the effect of complexation of the peptides with ionic graft copolymers with water-soluble graft chains was tested in this study. Amphiphilic anionic peptide E5 acquires membrane disrupting activity at acidic pH due to folding from the random coil state to an ordered α-helical structure. Aggregation and imprecise folding of the peptide limited membrane disrupting activity of the peptide. In the presence of a cationic graft copolymer, E5 and its analogs adopted an ordered conformation without aggregation. The mixture of the peptides and the copolymer functioned more efficiently than peptide alone at not only acidic pH but also neutral pH at which the peptide alone had no activity. Similarly, a cationic peptide was successfully folded and activated by an anionic graft copolymer. Thus, our analysis indicated that spontaneous nano-assembly of ionic peptides with graft copolymers having opposite ionic charges triggers the folding of peptides without loss of solubility, leading to enhanced bioactivity.
Keywords: Amphiphilic peptide; Cationic graft copolymer; Conformational change; Membrane disruption; Water-soluble complex.
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