Abstract
A strategy was described to design antimicrobial peptides (AMPs) with enhanced salt resistance and antiendotoxin activities by linking two helical AMPs with the Ala-Gly-Pro (AGP) hinge. Among the designed peptides, KR12AGPWR6 demonstrated the best antimicrobial activities even in high salt conditions (NaCl ~300 mM) and possessed the strongest antiendotoxin activities. These activities may be related to hydrophobicity, membrane-permeability, and α-helical content of the peptide. Amino acids of the C-terminal helices were found to affect the peptide-induced permeabilization of LUVs, the α-helicity of the designed peptides under various LUVs, and the LPS aggregation and size alternation. A possible model was proposed to explain the mechanism of LPS neutralization by the designed peptides. These findings could provide a new approach for designing AMPs with enhanced salt resistance and antiendotoxin activities for potential therapeutic applications.
Highlights
Antimicrobial peptides (AMPs) have been found in the innate defense systems of plants, insects, and animals [1,2,3,4,5]
We hypothesize that the binding and neutralization of LPS of cecropin and cecropin-like peptides is through similar structural features like S1-Nal-Nal
We have used peptide-induced permeabilization of large unilamellar vesicles (LUVs), Circular Dichroism (CD) spectroscopy, and LPS aggregation studies to investigate the factors attributed to the differences of antibacterial and antiendotoxin activities among KR12AGPKR6, KR12AGPWR6 and KR12AGPVR6
Summary
Antimicrobial peptides (AMPs) have been found in the innate defense systems of plants, insects, and animals [1,2,3,4,5]. Owing to these unique mechanisms, AMPs may be the solution to the problem of bacterial resistance [12,13] Problems such as salt sensitivity, cost of synthesis, bioavailability, and stability have limited the therapeutic applications of antimicrobial peptides [14,15]. Structure−activity relationships of P-113 and its derivatives were evaluated [38] Among these peptides, Bip-P-113 with the longest bulky non-nature amino acid sidechains was discovered to possess enhanced salt resistance, serum proteolytic stability, peptide-induced permeabilization, zeta potentials, LPS aggregation, and in vitro and in vivo LPS neutralizing activities. We hypothesize that the binding and neutralization of LPS of cecropin and cecropin-like peptides is through similar structural features like S1-Nal-Nal (i.e., amphipathic helix−linker−hydrophobic terminus). The antimicrobial and LPS neutralization activities of these designed peptides were determined
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
