Jya-Wei Cheng
National Tsing Hua University, Taiwan
Posters & Accepted Abstracts: J Infec Dis Treat
Antimicrobial peptides (AMPs) serve the first line of defense against invading pathogens and act by disrupting bacterial membrane integrity. Gram-negative bacteria cell wall is composed of two layers: the inner phospholipid membrane and the outer membrane with a highly conserved unique lipid called lipopolysaccharide (LPS; endotoxin). LPS acts as a permeability barrier against a number of bactericidal agents. Furthermore, LPS is well known as a potent inducer of the immune system when it is released to blood and often causes septic shock syndromes in human. Therefore, a potent antimicrobial agent shall not only possess antimicrobial activity but also have the ability to neutralize LPS and decrease its toxicity. Previously, we have designed a short tryptophan-rich peptide S1. However S1 has a low antimicrobial activity at high salt concentrations. We have developed an easy strategy to boost salt resistance and serum stability of short antimicrobial peptides by adding the non-nature bulky amino acid β-naphthylalanine to their C-termini. Herein, we have extended this study to characterize the anti-endotoxin effects of β-naphthylalanine end-tagged short antimicrobial peptides. Based on structure from transfer NOE (tr-NOE) and paramagnetic relaxation enhancement studies, we have found that S1-Nal-Nal positions itself deeply into LPS micelles, making the peptide more efficient in disrupting the LPS micelles than S1. Furthermore, the antiendotoxin activities of S1-Nal-Nal and S1 were compared based on in vitro and in vivo assays. The structural results will be used to help us design more potent antimicrobial peptides for clinical application in the future.
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