title: Rationally designed α-helical broad-spectrum antimicrobial peptides with idealized facial amphiphilicity.
abstract: A series of 12-amino acid peptide analogs is designed using point mutation strategy based on an α-helical peptide template. The first mutation in the series, KL12, has an idealized facial amphiphilicity. Subsequent mutations are performed to increase hydrophobic or cationic contents. Idealized facial amphiphilicity show enhanced antimicrobial activity and selectivity against most of the tested microbes. Increasing hydrophobic contents further enhance antimicrobial potency; however, selectivity of the most hydrophobic analog is impaired due to non-specific interactions with mammalian cell membrane. This study demonstrates that facial amphiphilicity and hydrophobic content are strongly correlated with antimicrobial activity and selectivity of antimicrobial peptides.
authors.affiliation: Institute of Bioengineering and Nanotechnology, 31 Biopolis Way, Singapore.
authors.forename: Nikken
authors.initials: N
authors.lastname: Wiradharma
authors.forename: Melvin Y S
authors.initials: MY
authors.lastname: Sng
authors.forename: Majad
authors.initials: M
authors.lastname: Khan
authors.forename: Zhan-Yuin
authors.initials: ZY
authors.lastname: Ong
authors.forename: Yi-Yan
authors.initials: YY
authors.lastname: Yang
mesh_terms: D000595:Amino Acid Sequence; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D017433:Protein Structure, Secondary
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides