Synthesis of low-hemolytic antimicrobial dehydropeptides based on gramicidin s.
The synthesis and biological activity of a novel cyclic beta-sheet-type antimicrobial dehydropeptide based on gramicidin S (GS) is described. The GS analogue, containing two (Z)-(beta-3-pyridyl)-alpha,beta-dehydroalanine (DeltaZ3Pal) residues at the 4 and 4' positions (2), was synthesized by solution-phase methodologies using Boc-Leu-DeltaZ3Pal azlactone. Analogue 2 exhibited high antimicrobial activity against Gram-positive bacteria and had much lower hemolytic activity than wild-type GS and the corresponding (Z)-alpha,beta-dehydrophenylalanine (DeltaZPhe) analogue (1).
Yamada
Keiichi
K
Department of Chemistry, Gunma University, Tenjin-cho, Kiryu, Gunma 376-8515, Japan.
Shinoda
Shun-suke
SS
Oku
Hiroyuki
H
Komagoe
Keiko
K
Katsu
Takashi
T
Katakai
Ryoichi
R
D000409:Alanine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002942:Circular Dichroism; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D006096:Gramicidin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006461:Hemolysis / Q000187:drug effects*; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D006096:Gramicidin; C015102:dehydroalanine; D000409:Alanine