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.