title: Inhibitory effects and mechanisms of physiological conditions on the activity of enantiomeric forms of an α-helical antibacterial peptide against bacteria.
abstract: Enantiomeric amphipathic α-helical antibacterial peptides were synthesized and their biophysical and biological properties under different physiological conditions were studied. In the absence of physiological factors, the L- and D-peptides exhibited similar antimicrobial activities against a broad spectrum of bacteria, even against clinical isolates with resistance to traditional antibiotics. However, in the presence of NaCl, CaCl₂ or human serum albumin (HSA) at physiological concentrations, the enantiomers revealed bacterium-species dependent attenuations in antibacterial activity. In the presence of salts the electrostatic interaction between the peptides and the biomembrane was inhibited. Salts, especially CaCl₂ weakened the ability of the peptides to permeabilize the outer membrane of Gram-negative bacteria, as determined by a 1-N-phenylnaphthylamine uptake assay. HSA exhibited variable inhibitory effects on the activity of the peptides when incubated with different bacterial strains. The peptides showed different binding association abilities to HSA at different molar ratios, regardless of their chirality, resulting in reduced peptide biological activity. The D-peptide performed better than its L-enantiomer in all conditions tested because of its resistance to proteolysis, and may therefore represent a promising candidate for development as a therapeutic agent.
authors.affiliation: Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, 2699 Qianjin Street, Changchun, Jilin 130012, China.
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Huang
authors.forename: Dianming
authors.initials: D
authors.lastname: Hao
authors.forename: Yu
authors.initials: Y
authors.lastname: Chen
authors.forename: Yimin
authors.initials: Y
authors.lastname: Xu
authors.forename: Juanjuan
authors.initials: J
authors.lastname: Tan
authors.forename: Yibing
authors.initials: Y
authors.lastname: Huang
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Chen
mesh_terms: D015057:1-Naphthylamine / Q000031:analogs & derivatives / Q000032:analysis; D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000037:antagonists & inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D002122:Calcium Chloride / Q000009:adverse effects / Q000494:pharmacology; D056148:Chromatography, Reverse-Phase; D002942:Circular Dichroism; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000254:growth & development; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000254:growth & development; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D011485:Protein Binding; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000009:adverse effects / Q000494:pharmacology; D012965:Sodium Chloride / Q000009:adverse effects / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D012709:Serum Albumin; D012965:Sodium Chloride; C005444:N-phenyl-1-naphthylamine; D015057:1-Naphthylamine; D002122:Calcium Chloride