title: Improvement of bacterial cell selectivity of melittin by a single Trp mutation with a peptoid residue.
abstract: To design melittin (ME) analogues that are not cytotoxic against mammalian cells but which possessing potent antimicrobial activity, we synthesized a ME analogue (ME-w) in which the Trp-19 residue of ME was replaced by a Trp-peptoid residue (Nhtrp). ME-w exhibited similar antimicrobial activity compared to ME against the tested six bacteria and C. albicans. However, it was much less cytotoxic against the hRBCs and HeLa and NIH-3T3 cells than ME. Tryptophan fluorescence and CD spectra revealed that the Trp-19 --> Nhtrp substitution in ME contributed to a much lower helical assembly in an aqueous environment and structural flexibility and exterior localization to zwitterionic membrane which modulates its selectivity toward bacterial cells.
authors.affiliation: Department of Bio-Materials, Graduate School and Research Center for Proteineous Materials, Chosun University, Gwangju 501-759, Korea.
authors.forename: Wan Long
authors.initials: WL
authors.lastname: Zhu
authors.forename: Yoonkyung
authors.initials: Y
authors.lastname: Park
authors.forename: Il-Seon
authors.initials: IS
authors.lastname: Park
authors.forename: Yong Sun
authors.initials: YS
authors.lastname: Park
authors.forename: Yangmee
authors.initials: Y
authors.lastname: Kim
authors.forename: Kyung-Soo
authors.initials: KS
authors.lastname: Hahm
authors.forename: Song Yub
authors.initials: SY
authors.lastname: Shin
mesh_terms: D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001419:Bacteria / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008555:Melitten / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008969:Molecular Sequence Data; D041681:NIH 3T3 Cells; D034444:Peptoids / Q000378:metabolism*; D014364:Tryptophan / Q000235:genetics* / Q000378:metabolism
chemical_list: D034444:Peptoids; D008555:Melitten; D014364:Tryptophan