title: Easy strategy to protect antimicrobial peptides from fast degradation in serum.
abstract: Antimicrobial peptides are promising novel peptide leads, but their low serum stability often limits their further consideration in drug development programs. Here, we describe a generally applicable strategy to stabilize peptides against serum proteases by replacing arginine residues with alpha-amino-3-guanidino-propionic acid (Agp). Peptide NH(2)-RRWRIVVIRVRR-CONH(2) was nearby totally degraded after 8 h in mouse serum, whereas the variant with Agp substituted was degraded less than 20%. The antimicrobial activity was not affected.
authors.affiliation: Institute for Bioanalytical Chemistry, Center for Biotechnology and Biomedicine (BBZ), Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, D-04103 Leipzig, Germany.
authors.forename: Daniel
authors.initials: D
authors.lastname: Knappe
authors.forename: Petra
authors.initials: P
authors.lastname: Henklein
authors.forename: Ralf
authors.initials: R
authors.lastname: Hoffmann
authors.forename: Kai
authors.initials: K
authors.lastname: Hilpert
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D023181:Antimicrobial Cationic Peptides / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D001120:Arginine / Q000737:chemistry; D004355:Drug Stability; D051379:Mice; D008826:Microbial Sensitivity Tests; D044967:Serum / Q000737:chemistry
chemical_list: D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001120:Arginine