Synthetic antimicrobial peptidomimetics with therapeutic potential.
A series of synthetic antimicrobial peptidomimetics (SAMPs) have been prepared and found to be highly active against several Gram-negative and Gram-positive bacterial strains. These derivatives comprise the minimal structural requirements for cationic antimicrobial peptides and showed high selectivity for Gram-negative and/or Gram-positive bacteria compared to human red blood cells. We have found that SAMPs share many of the attractive properties of cationic antimicrobial peptides inasmuch that a representative SAMP was found to insert into the bilayers of large unilamellar vesicles, permeabilized both the outer and cytoplasmic membrane of Escherichia coli ML-35p, and displayed an extremely rapid bacterial killing for Staphylococcus aureus. However, while antimicrobial peptides are prone to proteolytic degradation, high in vitro stability in human blood plasma was shown for SAMPs. A combination of high antibacterial activity against methicillin-resistant staphylococci and low toxicity against human erythrocytes makes these molecules promising candidates for novel antibacterial therapeutics.
Haug
Bengt Erik
BE
Department of Chemistry, University of Tromsø, N-9037 Tromsø, Norway. bengt-erik.haug@farm.uib.no
Stensen
Wenche
W
Kalaaji
Manar
M
Rekdal
Øystein
Ø
Svendsen
John S
JS
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis / Q000494:pharmacology* / Q000627:therapeutic use; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001769:Blood; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D013050:Spectrometry, Fluorescence
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides