Effects of single amino acid substitution on the biophysical properties and biological activities of an amphipathic α-helical antibacterial peptide against Gram-negative bacteria

• Published in: Molecules (Basel, Switzerland) Switzerland), 2014-07, Vol.19 (8), p.10803-10817
• Main Authors: Tan, Juanjuan, Huang, Jinfeng, Huang, Yibing, Chen, Yuxin
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Amino acids; Analogs; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antiinfectives and antibacterials; Antimicrobial Cationic Peptides - chemistry; Antimicrobial Cationic Peptides - pharmacology; antimicrobial peptide; Bacteria; Biological; biological activity; Cell Membrane Permeability - drug effects; Gram-negative bacteria; Gram-Negative Bacteria - drug effects; Helicity; Hemolysis - drug effects; Humans; Hydrophobic and Hydrophilic Interactions; Hydrophobicity; mechanism of action; Microbial Sensitivity Tests; Molecular Sequence Data; Peptides; Protein Binding; Protein Structure, Secondary
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules190810803

An antimicrobial peptide, known as V13K, was utilized as the framework to study the effects of charge, hydrophobicity and helicity on the biophysical properties and biological activities of α-helical peptides. Six amino acids (Lys, Glu, Gly, Ser, Ala, and Leu) were individually used to substitute the original hydrophobic valine at the selected sixteenth location on the non-polar face of V13K. The results showed that the single amino acid substitutions changed the hydrophobicity of peptide analogs as monitored by RP-HPLC, but did not cause significant changes on peptide secondary structures both in a benign buffer and in a hydrophobic environment. The biological activities of the analogs exhibited a hydrophobicity-dependent behavior. The mechanism of peptide interaction with the outer membrane and cytoplasmic membrane of Gram-negative bacteria was investigated. We demonstrated that this single amino acid substitution method has valuable potential for the rational design of antimicrobial peptides with enhanced activities.