Pap12-6 (trifluoroacetate salt)

Pap12-6 is an antibacterial peptide derived from the twelve N-terminal amino acids of the peptide papiliocin, which has been found in P. xuthus larvae.¹ It is active against a panel of eight Gram-negative bacteria, including E. coli, P. aeruginosa, and S. syphimurium (MIC₅₀s = 4-8 µM), and the Gram-positive bacteria S. aureus, methicillin-resistant S. aureus 3126 (MRSA-3126), B. subtilis, and S. epidermidis (MIC₅₀s = 4-8 µM) without affecting the viability of human erythrocytes, mouse RAW 264.7 macrophages, human HaCaT keratinocytes, or human HEK293 kidney cells at 25 µM. Pap12-6 induces membrane depolarization in E. coli when used at concentrations of 4 and 8 µM. Preincubation with Pap12-6 (10 µM) reduces nitrite (NO₂^-), Tnf-α, and Il-6 secretion levels in LPS-stimulated RAW 264.7 macrophages. In vivo, Pap12-6 (10 mg/kg) increases survival in mice infected with E. coli, as well as reduces the number of colony forming units (CFUs) in the lungs, liver, and kidneys in E. coli-infected mice when administered at a dose of 1 mg/kg. Pap12-6 (1 mg/kg) reduces serum aspartate aminotransferase (AST) and alanine transaminase (ALT) levels and blood urea nitrogen levels in a mouse model of E. coli-induced sepsis.