Improvement of bacterial cell selectivity of melittin by a single Trp mutation with a peptoid residue.
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.
Zhu
Wan Long
WL
Department of Bio-Materials, Graduate School and Research Center for Proteineous Materials, Chosun University, Gwangju 501-759, Korea.
Park
Yoonkyung
Y
Park
Il-Seon
IS
Park
Yong Sun
YS
Kim
Yangmee
Y
Hahm
Kyung-Soo
KS
Shin
Song Yub
SY
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
D034444:Peptoids; D008555:Melitten; D014364:Tryptophan