Structure-activity relationships of bacterial outer-membrane permeabilizers based on polymyxin B heptapeptides.
A series of cationic cyclic heptapeptides based on polymyxin B have been synthesized for use as permeabilizers of the outer membrane of Gram-negative bacteria. Only analogs with the Dab(2)-d-Phe(3)-Leu(4)-Xxx(5) sequence (Xxx = Dab or Orn) showed a synergistic bactericidal effect when combined with conventional antibiotics, indicating that the Dab(2) residue plays a critical role in permeation of the outer membrane of Gram-negative bacteria.
Urakawa
Hirotoshi
H
Department of Chemistry and Chemical Biology, Gunma University, 1-5-1 Tenjin-cho, Kiryu, Gunma 376-8515, Japan.
Yamada
Keiichi
K
Komagoe
Keiko
K
Ando
Setsuko
S
Oku
Hiroyuki
H
Katsu
Takashi
T
Matsuo
Ichiro
I
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002463:Cell Membrane Permeability / Q000187:drug effects*; D002942:Circular Dichroism; D004926:Escherichia coli / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011112:Polymyxin B / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D010456:Peptides, Cyclic; D011112:Polymyxin B