Proline residue-modified polycationic analogs of gramicidin S with high antibacterial activity against both Gram-positive and Gram-negative bacteria and low hemolytic activity.
Novel polycationic analogs of the cyclic decapeptide antibiotic, gramicidin S, possessing NH(2), D/L-Phe-NH or L-Lys-NH groups at the 4alpha- or 4beta-positions of the L-Pro residues, were synthesized. While L-Pro(4alpha/beta-NH(2))-containing analogs exhibited much weaker antibacterial activity, the D/L-Phe and L-Lys-substituted analogs exhibited higher antibacterial activity against Gram-negative bacteria than the parent gramicidin S. All of these additional amino group-containing analogs showed substantially reduced toxicity against human blood cells.
Kawai
M
M
Graduate School of Engineering, Nagoya Institute of Technology, Nagoya 466-8555, Japan. kawai@nitech.ac.jp
Yamamura
H
H
Tanaka
R
R
Umemoto
H
H
Ohmizo
C
C
Higuchi
S
S
Katsu
T
T
D000586:Amination; D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002412:Cations / Q000737:chemistry; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D004926:Escherichia coli / Q000187:drug effects*; D006096:Gramicidin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D010649:Phenylalanine / Q000737:chemistry; D011392:Proline / Q000737:chemistry*; D013211:Staphylococcus aureus / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D002412:Cations; D006096:Gramicidin; D010649:Phenylalanine; D011392:Proline