title: Relationship between peptide structure and antimicrobial activity as studied by de novo designed peptides.
abstract: As fundamental components in innate immunity, antimicrobial peptides (AMPs) hold great potentials in the treatment of persistent infections involving slow-growing or dormant bacteria in which, selective inhibition of prokaryotic bacteria in the context of eukaryotic cells is not only an essential requirement, but also a critical challenge in the development of antimicrobial peptides. To identify the sequence and structural properties critical for antimicrobial activity, a series of peptides varying in sequence, length, hydrophobicity/charge ratio, and secondary structure, were designed and synthesized. Their antimicrobial activities were then tested using Escherichia coli and HEK293 cells, together with several index activities against model membrane, including liposome leakage, fusion, and aggregation. While no evident correlation between the antimicrobial activity and the property of the peptides was observed, common activities against model membrane were nevertheless identified for the active antimicrobial peptides: mediating efficient membrane leakage, negligible membrane fusion and liposome aggregation. Therefore, in addition to identifying one highly active antimicrobial peptide, our study further sheds light on the design principle for these molecules.
authors.affiliation: Beijing National Laboratory for Molecular Sciences and the Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, 100871 China.
authors.forename: Jianbo
authors.initials: J
authors.lastname: Sun
authors.affiliation: School of Life Sciences and Technology, Xidian University, Xi'an, Shaanxi 710126, China.
authors.forename: Yuqiong
authors.initials: Y
authors.lastname: Xia
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100871, China. Electronic address: quan.du@pku.edu.cn.
authors.forename: Quan
authors.initials: Q
authors.lastname: Du
authors.affiliation: Beijing National Laboratory for Molecular Sciences and the Key Laboratory of Polymer Chemistry and Physics of Ministry of Education, College of Chemistry and Molecular Engineering, Peking University, 100871 China. Electronic address: dliang@pku.edu.cn.
authors.forename: Dehai
authors.initials: D
authors.lastname: Liang
keywords: Aggregation; Antimicrobial peptide; Fusion; Membrane leakage