Syntheses of low-hemolytic antimicrobial gratisin peptides

Makoto Tamaki; Manabu Kokuno; Ichiro Sasaki; Yumiko Suzuki; Michiko Iwama; Kenichi Saegusa; Yusuke Kikuchi; Mitsuno Shindo; Masahiro Kimura; Yoshiki Uchida

doi:10.1016/j.bmcl.2009.03.133

Syntheses of low-hemolytic antimicrobial gratisin peptides

Bioorg Med Chem Lett. 2009 May 15;19(10):2856-9. doi: 10.1016/j.bmcl.2009.03.133. Epub 2009 Mar 28.

Authors

Makoto Tamaki¹, Manabu Kokuno, Ichiro Sasaki, Yumiko Suzuki, Michiko Iwama, Kenichi Saegusa, Yusuke Kikuchi, Mitsuno Shindo, Masahiro Kimura, Yoshiki Uchida

Affiliation

¹ Department of Chemistry, Toho University, Funabashi, Chiba, Japan. tamaki@chem.sci.toho-u.ac.jp

PMID: 19369073
DOI: 10.1016/j.bmcl.2009.03.133

Abstract

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).

MeSH terms

Amino Acid Sequence
Anti-Bacterial Agents / chemical synthesis*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Gram-Negative Bacteria / drug effects
Gram-Positive Bacteria / drug effects
Hemolysis
Humans
Microbial Sensitivity Tests
Peptides / chemical synthesis
Peptides / chemistry
Peptides / toxicity
Peptides, Cyclic / chemical synthesis*
Peptides, Cyclic / chemistry*
Peptides, Cyclic / pharmacology
Peptides, Cyclic / toxicity
Structure-Activity Relationship

Substances

(D-Arg(6,6'))-gratisin
(D-Lys(6,6'))-gratisin
(D-Orn(6,6'))-gratisin
Anti-Bacterial Agents
Peptides
Peptides, Cyclic
gratisin