title: Effects of single amino acid substitution on the biophysical properties and biological activities of an amphipathic α-helical antibacterial peptide against Gram-negative bacteria.
abstract: 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.
authors: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.
authors: Juanjuan
authors: J
authors: Tan
authors: School of Life Sciences, Northeast Normal University, Changchun 130012, China.
authors: Jinfeng
authors: J
authors: Huang
authors: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China.
authors: Yibing
authors: Y
authors: Huang
authors: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, Changchun 130012, China. chen_yuxin@jlu.edu.cn.
authors: Yuxin
authors: Y
authors: Chen
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides