Easy strategy to protect antimicrobial peptides from fast degradation in serum.
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.
Knappe
Daniel
D
Institute for Bioanalytical Chemistry, Center for Biotechnology and Biomedicine (BBZ), Faculty of Chemistry and Mineralogy, Universität Leipzig, Deutscher Platz 5, D-04103 Leipzig, Germany.
Henklein
Petra
P
Hoffmann
Ralf
R
Hilpert
Kai
K
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
D000890:Anti-Infective Agents; D023181:Antimicrobial Cationic Peptides; D001120:Arginine