Dependence on size and shape of non-nature amino acids in the enhancement of lipopolysaccharide (LPS) neutralizing activities of antimicrobial peptides
Journal
Journal of Colloid and Interface Science
Journal Volume
533
Pages
492-502
Date Issued
2019
Author(s)
Chih, Ya-Han ; Wang, Siou-Ying ; Cheng, Kuang-Ting ; Hsu, Su-Ya ; Wu, Chih-Lung ; Yu, Hui-Yuan ; Cheng, Jya-Wei
Abstract
Hypothesis: Release of lipopolysaccharides (LPS) from bacteria into bloodstream may cause serious unwanted stimulation of the host immune system. P-113 is a clinically active histidine-rich antimicrobial peptide. Nal-P-113, a β-naphthylalanine-substituted P-113, is salt-resistant but has limited LPS neutralizing activity. We suspected the size and shape of the non-natural bulky amino acid may affect its LPS neutralizing activity. Herein, antimicrobial, LPS neutralizing, and antiproteolytic effects of phenylalanine- (Phe-P-113), β-naphthylalanine- (Nal-P-113), β-diphenylalanine- (Dip-P-113), and β-(4,4′-biphenyl)alanine- (Bip-P-113) substituted P-113 were studied. Experiments: Structure-activity relationships of P-113, Phe-P-113, Nal-P-113, Dip-P-113, and Bip-P-113 were evaluated using antimicrobial activity assays, serum proteolytic assays, peptide-induced permeabilization of large unilamellar vesicles, zeta potential measurements, dynamic light scattering measurement of LPS aggregation, and Limulus amebocyte lysate assays for measuring LPS neutralization. In vitro and in vivo LPS neutralizing activities were further confirmed by LPS-induced inflammation inhibition in an endotoxemia mouse model. Findings: Bip-P-113 and Dip-P-113 had the longest and widest non-nature amino acids, respectively. Bip-P-113 enhanced salt resistance, serum proteolytic stability, peptide-induced permeabilization, zeta potential measurements, LPS aggregation, and in vitro and in vivo LPS neutralizing activities. These results could help design novel antimicrobial peptides that have enhanced stability in vivo and that can have potential therapeutic applications. ? 2018 Elsevier Inc.
Subjects
Antimicrobial peptide; Lipopolysaccharide (LPS) neutralization; Non-natural amino acid; Salt resistance
SDGs
Other Subjects
Acid resistance; Body fluids; Light scattering; Microorganisms; Peptides; Polypeptides; Zeta potential; Antimicrobial peptide; Dynamic light scattering measurement; Large unilamellar vesicles; Lipopolysaccharides; Non natural amino acids; Salt resistance; Structure activity relationships; Zeta potential measurements; Amino acids; bacterium lipopolysaccharide; beta (4,4' biphenyl)alanine p 113; beta diphenylalanine p 113; beta naphthylalanine p 113; phenylalanine p 113; polypeptide antibiotic agent; proteinase inhibitor; saralasin; tumor necrosis factor; unclassified drug; amino acid; antiinfective agent; antimicrobial cationic peptide; endotoxin; lipopolysaccharide; animal experiment; animal model; animal tissue; antimicrobial activity; Article; cell membrane permeability; controlled study; cytokine production; dilution; dose response; drug bioavailability; drug cytotoxicity; drug design; drug synthesis; hemolysis; human; human cell; hydrophobicity; in vitro study; in vivo study; Limulus lysate test; lipopolysaccharide-induced endotoxemia; lipopolysaccharide-induced lung inflammation; male; minimum inhibitory concentration; mouse; nonhuman; particle size; phospholipid vesicle; photon correlation spectroscopy; priority journal; protein degradation; structure activity relation; surface charge; zeta potential; animal; antagonists and inhibitors; blood; C57BL mouse; chemically induced; chemistry; disease model; drug effect; endotoxemia; Escherichia coli; fibroblast; hemolytic plaque assay; inflammation; microbial sensitivity test; particle size; Pseudomonas aeruginosa; Staphylococcus aureus; surface property; Amino Acids; Animals; Anti-Bacterial Agents; Antimicrobial Cationic Peptides; Disease Models, Animal; Dose-Response Relationship, Drug; Dynamic Light Scattering; Endotoxemia; Endotoxins; Escherichia coli; Fibroblasts; Hemolytic Plaque Technique; Humans; Inflammation; Lipopolysaccharides; Male; Mice; Mice, Inbred C57BL; Microbial Sensitivity Tests; Particle Size; Pseudomonas aeruginosa; Staphylococcus aureus; Structure-Activity Relationship; Surface Properties
Type
journal article