Antibiotic-resistant
bacterial infections have increased
the prevalence
of sepsis and septic shock mortality worldwide and have become a global
concern. Antimicrobial peptides (AMPs) show remarkable properties
for developing new antimicrobial agents and host response modulatory
therapies. A new series of AMPs derived from pexiganan (MSI-78) were
synthesized. The positively charged amino acids were segregated at
their N- and C-termini, and the rest of the amino acids created a
hydrophobic core surrounded by positive charges and were modified
to simulate the lipopolysaccharide (LPS). The peptides were investigated
for their antimicrobial activity and LPS-induced cytokine release
inhibition profile. Various biochemical and biophysical methods were
used, including attenuated total reflection Fourier transform infrared
(ATR-FTIR) spectroscopy, microscale thermophoresis (MST), and electron
microscopy. Two new AMPs, MSI-Seg-F2F and MSI-N7K, preserved their
neutralizing endotoxin activity while reducing toxicity and hemolytic
activity. Combining all of these properties makes the designed peptides
potential candidates to eradicate bacterial infection and detoxify
LPS, which might be useful for sepsis treatment.