Modification of a synthetic antimicrobial peptide (ESF1) for improved inhibitory activity.
Rational modification of an existing cationic alpha-helical antimicrobial peptide (ESF1) for improved activity by increasing amphipathicity was undertaken. ESF1 and two variants (GR7 and SA3) were synthesized and tested for activity range, minimum inhibitory concentration, and hemolytic activity. Biological activity was related to structure as determined by circular dichroism. The substitution of arginine for glycine in position seven was found to increase antimicrobial activity without effecting hemolysis. Increased activity was related to stronger alpha-helix formation in buffer. Increased beta-sheet formation in micellar SDS was observed and speculated to be due to a stronger ability of the variants to form multimolecule complexes, a feature consistent with existing models of cationic peptide activity.
Dykes
G A
GA
Department of Genetics, University of Natal, Scottsville, 3201, South Africa. dykesg@gene.unp.ac.za
Aimoto
S
S
Hastings
J W
JW
D000595:Amino Acid Sequence; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D000890:Anti-Infective Agents / Q000138:chemical synthesis; D002942:Circular Dichroism; D004912:Erythrocytes / Q000187:drug effects; D006461:Hemolysis / Q000187:drug effects; D006801:Humans; D008968:Molecular Conformation; D008969:Molecular Sequence Data; D010455:Peptides / Q000737:chemistry; D017433:Protein Structure, Secondary; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D000890:Anti-Infective Agents; D010455:Peptides; D012967:Sodium Dodecyl Sulfate