Structure–activity relationship study of amphipathic antimicrobial peptides using helix‐destabilizing sarcosine. (23rd June 2021)

• Record Type: Journal Article
• Authors: Yokoo, Hidetomo; Hirano, Motoharu; Ohoka, Nobumichi; Misawa, Takashi; Demizu, Yosuke
• Is Part Of: Journal of peptide science. Volume 27:Number 12(2021)
• Page Start: n/a
• Page End: n/a
• Publication Date: 2021-06-23
• Subjects: amphipathicity -- antimicrobial peptides -- helical structures -- sarcosine; Peptides -- Periodicals; Peptides -- Periodicals; 572.65
• DOI: 10.1002/psc.3360
• Languages: English
• ISSNs: 1075-2617

Abstract

Abstract : 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 ) (DH5 α ) cells. The activity against E. coli (DH5 α ) 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. Abstract : The sarcosine substitutions provide an approach to study the structure‐5activity relationship of helical AMPs, and the helicity of Stripe .