title: Guanidylation and tail effects in cationic antimicrobial lipopeptoids.
abstract: BACKGROUND
  Cationic antimicrobial peptides (CAMPs) are attractive scaffolds for the next generation of antimicrobial compounds, due to their broad spectrum of activity against multi-drug resistant bacteria and the reduced fitness of CAMP-insensitive mutants. Unfortunately, they are limited by poor in vivo performance, including ready cleavage by endogenous serum proteases.
  
  
  RESULTS
  To explore the potential for peptoid residues to replace well studied CAMP scaffolds we have produced a series of antimicrobial lipopeptoids, with sequences similar to previously reported lipopeptides. The activity of the peptoids was assessed against a panel of clinically relevant and laboratory reference bacteria, and the potential for non-specific binding was determined through hemolytic testing and repeating the antimicrobial testing in the presence of added bovine serum albumin (BSA). The most active peptoids displayed good to moderate activity against most of the gram positive strains tested and moderate to limited activity against the gram negatives. Antimicrobial activity was positively correlated with toxicity towards eukaryotic cells, but was almost completely eliminated by adding BSA.
  
  
  CONCLUSIONS
  The lipopeptoids had similar activities to the previously reported lipopeptides, confirming their potential to act as replacement, proteolytically stable scaffolds for CAMPs.
authors: Department of Chemistry, University of Manitoba, Winnipeg, Manitoba, Canada.
authors: Brandon
authors: B
authors: Findlay
authors: Paul
authors: P
authors: Szelemej
authors: George G
authors: GG
authors: Zhanel
authors: Frank
authors: F
authors: Schweizer
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D001419:Bacteria / Q000187:drug effects; D002417:Cattle; D019791:Guanidine / Q000737:chemistry*; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008826:Microbial Sensitivity Tests; D034444:Peptoids / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D023181:Antimicrobial Cationic Peptides; D034444:Peptoids; D019791:Guanidine