title: Structure-activity relationship of indolicidin, a Trp-rich antibacterial peptide.
abstract: A series of Trp and Arg analogs of antibacterial indolicidin (Ind) was synthesized and the antimicrobial and hemolytic activities were investigated. [L(9)]Ind, [L(11)]Ind, [K(8),L(9)]Ind and [K(6, 8),L(9)]Ind showed desirable characteristics, exhibiting negligible hemolytic activity while keeping strong antibacterial activity. The results indicated that the Trp residue at position 11 essentially contributes to both activities and one can not be exchanged for the other, whereas the Trp residues at positions 4 and 9 play important roles in antimicrobial and hemolytic activities, respectively. The Trp residues at positions 6 and 8 play no important roles in biological activities. We then found that the retro analog of Ind showed higher antibacterial activity than Ind against both Gram-positive and Gram-negative bacteria but remarkably lower hemolytic activity than that of Ind.
authors.affiliation: Department of Chemistry, Faculty of Science, Fukuoka University, Jonan-ku, Fukuoka, Japan. andos@fukuoka-u.ac.jp
authors.forename: Setsuko
authors.initials: S
authors.lastname: Ando
authors.forename: Keitarou
authors.initials: K
authors.lastname: Mitsuyasu
authors.forename: Yoshitake
authors.initials: Y
authors.lastname: Soeda
authors.forename: Mariko
authors.initials: M
authors.lastname: Hidaka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ito
authors.forename: Kouki
authors.initials: K
authors.lastname: Matsubara
authors.forename: Mitsuno
authors.initials: M
authors.lastname: Shindo
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Uchida
authors.forename: Haruhiko
authors.initials: H
authors.lastname: Aoyagi
mesh_terms: D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology*; D002850:Chromatography, Gel; D002942:Circular Dichroism; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship; D014364:Tryptophan / Q000737:chemistry*
chemical_list: D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; C073143:indolicidin; D014364:Tryptophan