Antibacterial Activities of Short Designer Peptides: a Link between Propensity for Nanostructuring and Capacity for Membrane Destabilization

• Published in: Biomacromolecules Vol. 11; no. 2; pp. 402 - 411
• Main Authors: Chen, Cuixia, Pan, Fang, Zhang, Shengzhong, Hu, Jing, Cao, Meiwen, Wang, Jing, Xu, Hai, Zhao, Xiubo, Lu, Jian R
• Format: Journal Article
• Language: English
• Published: Washington, DC American Chemical Society 08.02.2010
• Subjects: Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacokinetics; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Applied sciences; Biological and medical sciences; Cell Membrane - drug effects; Cell Membrane - metabolism; Dose-Response Relationship, Drug; Escherichia coli - drug effects; Escherichia coli - metabolism; Exact sciences and technology; Humans; Medical sciences; Nanostructures - chemistry; Natural polymers; Peptides - chemistry; Peptides - pharmacokinetics; Pharmacology. Drug treatments; Physicochemistry of polymers; Proteins; Staphylococcus aureus - drug effects; Staphylococcus aureus - metabolism; Biological properties; Hemolysis; Peptides; Membrane interaction; Escherichia coli; Phospholipid; Artificial membrane; Experimental study; Amphiphilic compound; Bactericidal effect; Membrane transport; Plasma membrane; Bacteria; Micrococcales; Micrococcaceae; Molecular aggregation; Peptide synthesis; Aqueous solution; Antibacterial agent; Mechanism of action; Staphylococcus aureus; Enterobacteriaceae
• ISSN: 1525-7797; 1526-4602
• DOI: 10.1021/bm901130u

Amphiphilic peptides A3K, A6K, and A9K displayed an increasing propensity for nanoaggregation with increasing the size of hydrophobic alanine moiety, and the size and shape of the aggregates showed a steady transition from loose peptide stacks formed by A3K, long nanofibers by A6K, to short and narrow nanorods by A9K. This size and shape transition was broadly consistent with the trend predicted from interfacial packing and curvature change if these peptide surfactants were treated as conventional surfactants. The antibacterial capacity, defined by the killing of percentage of bacteria in a given time and peptide concentration, showed a strong correlation to peptide hydrophobicity, evident from both microscopic and fluorescence imaging studies. For A9K, the power for membrane permeation and bacterial clustering intensified with peptide concentration and incubation time. These results thus depict a positive correlation between the propensity for self-assembly of the peptides, their membrane penetration power, and bactericidal capacity. Although the exposure of A9K to a preformed DPPC membrane bilayer showed little structural disturbance, the same treatment to the preformed DPPG membrane bilayer led to substantial disruption of model membrane structure, a trend entirely consistent with the high selectivity observed from membrane hemolytic studies.