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• W2587048925 abstract "Previously, we showed that the antimicrobial cationic and amphipathic octadecapeptide AmyI‐1‐18 from rice α ‐amylase (AmyI‐1) inhibited the endotoxic activity of lipopolysaccharide (LPS) from Escherichia coli . In addition, we demonstrated that several AmyI‐1‐18 analogs containing arginine or leucine substitutions, which were designed on the basis of the helical wheel projection of AmyI‐1‐18, exhibited higher antimicrobial activity against human pathogenic microorganisms than AmyI‐1‐18. In the present study, anti‐inflammatory (anti‐endotoxic) activities of five AmyI‐1‐18 analogs containing arginine or leucine substitutions were investigated. Two single arginine‐substituted and two single leucine‐substituted AmyI‐1‐18 analogs inhibited the production of LPS‐induced nitric oxide in mouse macrophages (RAW264) more effectively than AmyI‐1‐18. These data indicate that enhanced cationic and hydrophobic properties of AmyI‐1‐18 are associated with improved anti‐endotoxic activity. In subsequent chromogenic Limulus amebocyte lysate assays, 50% inhibitory concentrations (IC 50 ) of the three AmyI‐1‐18 analogs (G12R, D15R, and E9L) were 0.11–0.13 μ m , indicating higher anti‐endotoxic activity than that of AmyI‐1‐18 (IC 50, 0.22 μ m ), and specific LPS binding activity. In agreement, surface plasmon resonance analyses confirmed direct LPS binding of three AmyI‐1‐18 analogs. In addition, AmyI‐1‐18 analogs exhibited little or no cytotoxic activity against RAW264 cells, indicating that enhancements of anti‐inflammatory and LPS‐neutralizing activities following replacement of arginine or leucine did not result in significant increases in cytotoxicity. This study shows that the arginine‐substituted and leucine‐substituted AmyI‐1‐18 analogs with improved anti‐endotoxic and antimicrobial activities have clinical potential as dual‐function host defense agents. Copyright © 2017 European Peptide Society and John Wiley & Sons, Ltd." @default.
• W2587048925 created "2017-02-17" @default.
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• W2587048925 date "2017-02-10" @default.
• W2587048925 modified "2023-09-29" @default.
• W2587048925 title "Effects of arginine and leucine substitutions on anti-endotoxic activities and mechanisms of action of cationic and amphipathic antimicrobial octadecapeptide from rice<i>α</i>-amylase" @default.
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• W2587048925 doi "https://doi.org/10.1002/psc.2983" @default.
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