Preparation and properties of novel gramicidin S analogs possessing a tri-, tetra- or pentamethylene bridge between ornithine side chains.
Gramicidin S (GS) analogs in which the Ndelta atoms of the two Orn side chains are linked by an oligomethylene bridge [-(CH2)n-; n=3-5] were prepared via the bis(p-nitrobenzenesulfonyl) derivative [Orn(NBS)2,2']GS. For comparison the nonbridged secondary amino group-containing analog [Orn(Me)2,2']GS was also prepared. 1H NMR and CD spectral analysis indicated that these analogs adopt the same beta-sheet conformation as GS. The antimicrobial activities of these analogs were very similar, but were slightly dependent on the bridge chain length, the trimethylene-bridged analog being the most potent.
Yamada
K
K
Department of Applied Chemistry, Nagoya Institute of Technology, Japan.
Ando
K
K
Takahashi
Y
Y
Oda
Y
Y
Yamamura
H
H
Araki
S
S
Kobayashi
K
K
Katakai
R
R
Kato
F
F
Kawai
M
M
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001412:Bacillus subtilis / Q000187:drug effects; D002942:Circular Dichroism; D004353:Drug Evaluation, Preclinical; D004926:Escherichia coli / Q000187:drug effects; D006096:Gramicidin / Q000031:analogs & derivatives* / Q000737:chemistry*; D006838:Hydrocarbons; D009682:Magnetic Resonance Spectroscopy; D008697:Methane / Q000031:analogs & derivatives / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009952:Ornithine / Q000737:chemistry; D011487:Protein Conformation; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006838:Hydrocarbons; D006096:Gramicidin; C030011:carbene; D009952:Ornithine; D008697:Methane