Antimicrobial Peptides with Enhanced Salt Resistance and Antiendotoxin Properties

• Published in: International journal of molecular sciences Vol. 21; no. 18; p. 6810
• Main Authors: Chu, Hung-Lun, Chih, Ya-Han, Peng, Kuang-Li, Wu, Chih-Lung, Yu, Hui-Yuan, Cheng, Doris, Chou, Yu-Ting, Cheng, Jya-Wei
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI 16.09.2020; MDPI AG
• Subjects: Amino Acid Sequence; Animals; antiendotoxin; antimicrobial peptide; cecropin-like; Colony Count, Microbial; Drug Evaluation, Preclinical; Endotoxemia - drug therapy; Gram-Negative Bacteria - drug effects; Gram-Positive Bacteria - drug effects; Humans; Hydrophobic and Hydrophilic Interactions; Limulus Test; lipopolysaccharide; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - toxicity; Male; Mice; Mice, Inbred C57BL; Pore Forming Cytotoxic Proteins - chemical synthesis; Pore Forming Cytotoxic Proteins - pharmacology; Pore Forming Cytotoxic Proteins - therapeutic use; Protein Conformation, alpha-Helical; salt resistance; Salt Tolerance - drug effects; Sodium Chloride - pharmacology; Structure-Activity Relationship; Tumor Necrosis Factor-alpha - blood; Unilamellar Liposomes; cecropin-like; antimicrobial peptide; lipopolysaccharide; salt resistance; antiendotoxin
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms21186810

A strategy was described to design antimicrobial peptides (AMPs) with enhanced salt resistance and antiendotoxin activities by linking two helical AMPs with the Ala-Gly-Pro (AGP) hinge. Among the designed peptides, KR12AGPWR6 demonstrated the best antimicrobial activities even in high salt conditions (NaCl ~300 mM) and possessed the strongest antiendotoxin activities. These activities may be related to hydrophobicity, membrane-permeability, and α-helical content of the peptide. Amino acids of the C-terminal helices were found to affect the peptide-induced permeabilization of LUVs, the α-helicity of the designed peptides under various LUVs, and the LPS aggregation and size alternation. A possible model was proposed to explain the mechanism of LPS neutralization by the designed peptides. These findings could provide a new approach for designing AMPs with enhanced salt resistance and antiendotoxin activities for potential therapeutic applications.