Discovery of potent antimicrobial peptide analogs of Ixosin-B

• Published in: Bioorganic & medicinal chemistry letters Vol. 22; no. 12; pp. 4185 - 4188
• Main Authors: Lung, Feng-Di T., Wang, Kai-Shiuan, Liao, Zih-Jie, Hsu, Sheng-Kai, Song, Fei-Yi, Liou, Chien-Chung, Wu, Yu-Shan
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15.06.2012; Elsevier
• Subjects: amides; Amino Acid Sequence; Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Antimicrobial activity; Antimicrobial agents; Antimicrobial Cationic Peptides - chemical synthesis; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Biological and medical sciences; Erythrocytes; Erythrocytes - drug effects; Escherichia coli; Escherichia coli - drug effects; Escherichia coli - growth & development; Hemolysis; Hemolytic activity; Infection; Ixosin-B; Medical sciences; Microbial Sensitivity Tests; Microbial Viability - drug effects; Molecular Sequence Data; Pathogens; Pharmacology. Drug treatments; Protein Structure, Secondary; Pseudomonas aeruginosa; Pseudomonas aeruginosa - drug effects; Pseudomonas aeruginosa - growth & development; Staphylococcus aureus; Staphylococcus aureus - drug effects; Staphylococcus aureus - growth & development; Structure-Activity Relationship; Antimicrobial activity; Hemolytic activity; Ixosin-B; Antimicrobial peptides; Hemolysis; Toxicity; Red blood cell; Cytotoxicity; Biological activity; Antimicrobial agent; Antimicrobial peptide
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2012.04.018

Antimicrobial peptides (AMPs) are recognized as a potential alternative class of antimicrobial agents because of their selectivity for prokaryotic cells and promise of minimizing the development of bacterial resistance. We developed a lead 11-mer peptide, KRLRRVWRRWR-amide (Fig. 1), which exhibited potent antimicrobial activity and no hemolytic activity. Antimicrobial peptides (AMPs) represent the first defense line against infection when organisms are infected by pathogens. These peptides are generally good targets for the development of antimicrobial agents. Peptide amide analogs of Ixosin-B, an antimicrobial peptide with amino acid sequence of QLKVDLWGTRSGIQPEQHSSGKSDVRRWRSRY, were designed, synthesized and examined for antimicrobial activities against Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa. Within the peptides synthesized, we discovered an 11-mer peptide, KRLRRVWRRWR-amide, which exhibited potent antimicrobial activity while very little hemolytic activity in human erythrocytes was observed even at high dose level (100μM). With further modifications, this peptide could be developed into a potent antimicrobial agent in the future.