title: Polycationic gramicidin S analogues with both high antibiotic activity and very low hemolytic activity.
abstract: The substitution of each constituent amino acid residue of gramicidin S (GS), cyclo(-Val(1,1')-Orn(2,2')-Leu(3,3')-D-Phe(4,4')-Pro(5,5')-)(2) with Lys residue indicated that each side chain structure of the constituent amino acid residues affect largely the antibiotic activity and hemolytic activity of GS. Further, the substitution of D-Phe(4,4') and Pro(5,5') residues with basic amino acid residues as a Lys residue results the high antibiotic activity and the very low hemolytic activity. Thus, we have found novel positions on the scaffold of GS at D-Phe(4,4') and Pro(5,5') residues whose modification will significantly increase the therapeutic index.
authors.affiliation: Department of Chemistry, Toho University, Funabashi, Chiba 274-8510, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Tamaki
authors.forename: Takuji
authors.initials: T
authors.lastname: Harada
authors.forename: Kenta
authors.initials: K
authors.lastname: Fujinuma
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Takanashi
authors.forename: Mitsuno
authors.initials: M
authors.lastname: Shindo
authors.forename: Masahiro
authors.initials: M
authors.lastname: Kimura
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Uchida
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D004912:Erythrocytes / Q000187:drug effects; D006096:Gramicidin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects*; D012756:Sheep
chemical_list: D000900:Anti-Bacterial Agents; D006096:Gramicidin