Antimicrobial peptides (AMPs) are potential therapeutic agents against bacteria. We recently showed that a rationally designed AMP, termed Stripe, with an amphipathic distribution of native cationic and hydrophobic amino acids on its helical structure exhibited potent antimicrobial activity against Gram-positive and Gram-negative bacteria with negligible hemolytic activity and cytotoxicity. In this study, the structure-activity relationship of Stripe was elucidated by designing a series of antimicrobial peptides whereby amino acid residues of Stripe were exchanged with helix-destabilizing sarcosine residues. Stripe 1-5 peptides with hydrophobic amino acids substituted with sarcosine were predominantly unstructured and showed no antimicrobial activity, except against Escherichia coli (E. coli) (DH5α) cells. The activity against E. coli (DH5α) cells and the helicity of Stripe 1-5 peptides decreased concomitantly as the number of sarcosine residue substitutions increased. Stripe 1-5 peptides showed no hemolytic activity or cytotoxicity. The results indicate that sarcosine substitutions provide an approach to study the structure-activity relationship of helical AMPs, and the helicity of Stripe is an important feature defining its activity.
Keywords: amphipathicity; antimicrobial peptides; helical structures; sarcosine.
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