Structure-Activity Relationship Study of Helix-Stabilized Antimicrobial Peptides Containing Nonproteinogenic Amino Acids

Helical amphipathic peptides containing cationic andhydrophobicamino acid residues can possess potent antimicrobial activity againstboth Gram-positive and Gram-negative bacteria. In this study, severalamphipathic peptides with enhanced helical structures containing nonproteinogenicamino acids were designed, and the relationships between the antimicrobialactivity, hemolytic activity, and cytotoxicity were evaluated. Inparticular, the effect on the antimicrobial activity and cytotoxicityof the number and position of stapling structures introduced intothe sequence was investigated. Peptide stp1 containing & alpha;,& alpha;-disubstituted amino acids showed potent antimicrobialactivity against multidrug-resistant bacteria (MDRP, SP45, and Staphylococcus aureus) without causing appreciablehemolytic activity or cytotoxicity. The cytotoxicity was found tobe somewhat correlated to the hydrophobicity of the peptides.

Automated summary

In this study, helical amphipathic peptides containing nonproteinogenic amino acids were designed to enhance antimicrobial activity. The relationships between antimicrobial activity, hemolytic activity, and cytotoxicity were evaluated. Peptide stp1, containing α,α-disubstituted amino acids, showed potent antimicrobial activity against multidrug-resistant bacteria without causing appreciable hemolytic activity or cytotoxicity.