Syntheses of low-hemolytic antimicrobial gratisin peptides.
Antibiotic and hemolytic activities of gratisin (GR), cyclo(-Val(1)-Orn(2)-Leu(3)-d-Phe(4)-Pro(5)-d-Tyr(6)-)(2), and fifteen GR analogues, which have various d-amino acid residues in place of d-Tyr(6,6') residues, were examined. Among them, [d-Orn(6,6')]-GR, [d-Lys(6,6')]-GR and [d-Arg(6,6')]-GR showed the strong activity against both Gram-positive and Gram-negative bacteria. In addition, the antibiotics showed significantly reduced toxicity against human blood cells compared with gramicidin S, cyclo(-Val(1)-Orn(2)-Leu(3)-d-Phe(4)-Pro(5)-)(2).
Department of Chemistry, Toho University, Funabashi, Chiba, Japan. tamaki@chem.sci.toho-u.ac.jp
Makoto
M
Tamaki
Manabu
M
Kokuno
Ichiro
I
Sasaki
Yumiko
Y
Suzuki
Michiko
M
Iwama
Kenichi
K
Saegusa
Yusuke
Y
Kikuchi
Mitsuno
M
Shindo
Masahiro
M
Kimura
Yoshiki
Y
Uchida
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006461:Hemolysis; D006801:Humans; D008826:Microbial Sensitivity Tests; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D010456:Peptides, Cyclic / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
C541591:(D-Arg(6,6'))-gratisin; C541590:(D-Lys(6,6'))-gratisin; C541589:(D-Orn(6,6'))-gratisin; D000900:Anti-Bacterial Agents; D010455:Peptides; D010456:Peptides, Cyclic; C033282:gratisin