Immunogenicity and pharmacokinetics of short, proline-rich antimicrobial peptides. (August 2015)

• Record Type: Journal Article
• Authors: Holfeld, Luzia; Herth, Nicole; Singer, David; Hoffmann, Ralf; Knappe, Daniel
• Is Part Of: Future medicinal chemistry. Volume 7:Number 12(2015)
• Page Start: 1581
• Page End: 1596
• Publication Date: 2015-08
• Subjects: Pharmaceutical chemistry -- Periodicals; 615.19005
• DOI: 10.4155/fmc.15.91
• Languages: English
• ISSNs: 1756-8919

Abstract

Aim: The potential of proline-rich antimicrobial peptides (PrAMPs) to treat multidrug-resistant Gram-negative pathogens has been intensively investigated. They are efficacious at low doses in infection models and well tolerated in healthy mice at high doses.Methods & results: PrAMPs Onc72 and Api88 were nonimmunogenic in mice unless conjugated to a carrier protein. Monoclonal IgG1 /IgG2b antibodies produced by hybridoma cells were mapped to different Onc72 regions and combined in a sandwich-ELISA in a pharmacokinetic study. Onc72 was detected at concentrations up to 32 µg/ml in murine blood after administering 20 mg/kg and reached several organs within 10 min.Conclusion: Both PrAMPs were not immunogenic and Onc72 concentrations in blood were well above the minimal inhibitory concentrations for Enterobacteriaceae further confirming their potential as novel antibiotics.