title: Tuning the antimicrobial pharmacophore to enable discovery of short lipopeptides with multiple modes of action.
abstract: Tryptophan and arginine rich antimicrobial peptides (AMPs) possess high potencies against both gram positive and gram negative bacteria, while lipopeptides represent another family of promising antimicrobial agents to combat invading pathogens. In the present study, we have synthesized a series of very short arginine, lysine and tryptophan containing lipopeptides and evaluated their antimicrobial activities against a panel of pathogenic microorganisms including Staphylococcus aureus, Escherichia coli, and Candida albicans. The results showed that most of these peptides were effective against tested strains with MIC values ranging from 3.9 to 62.5 μg/mL. In addition to the small size, potent bactericidal activity, low to moderate hemolytic toxicity and membrane disruption ability, several peptides such as C10-RIKWWK and C10-RKWWK apparently retarded the migration of DNA on agarose gel in the DNA-binding assay, which implied the multiple modes of action in their bacteria-killing mechanism. These peptides revealed a promising therapeutic potential to develop as new antimicrobial agents.
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Yuxin
authors.initials: Y
authors.lastname: Fang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Wenjing
authors.initials: W
authors.lastname: Zhong
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Tianrong
authors.initials: T
authors.lastname: Xun
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Dongguo
authors.initials: D
authors.lastname: Lin
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Wenjun
authors.initials: W
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Jingyu
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lv
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China. Electronic address: liusw@smu.edu.cn.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Southern Medical University, 1838 Guangzhou Avenue North, Guangzhou 510515, PR China. Electronic address: jianhe@smu.edu.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: He
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002176:Candida albicans / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D015195:Drug Design; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000166:cytology / Q000187:drug effects; D006367:HeLa Cells; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D055666:Lipopeptides / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013211:Staphylococcus aureus / Q000166:cytology / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000890:Anti-Infective Agents; D055666:Lipopeptides
keywords: Antimicrobial agents; Multiple modes of action; Short lipopeptides