Design and Synthesis of Lipopolysaccharide-Binding Antimicrobial Peptides Based on Truncated Rabbit and Human CAP18 Pept
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Design and Synthesis of Lipopolysaccharide-Binding Antimicrobial Peptides Based on Truncated Rabbit and Human CAP18 Peptides and Evaluation of Their Action Mechanism Hamid Madanchi 1,2 & Ramin Ebrahimi Kiasari 2 & Seyed Javad Seyed Mousavi 2 & Behrooz Johari 3 & Ali Akbar Shabani 1 & Soroush Sardari 2
# Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract Lipopolysaccharide (LPS) is a toxic and immunogenic agent for human. Additionally, LPS is a good target for some antimicrobial compounds, including antimicrobial peptides (AMPs). LPS-binding peptides (LBPs) can recognize and neutralize LPS. Rabbit and human cathelicidins are AMPs with LPS-binding activity. In this study, we designed and synthesized two new truncated LBPs from rabbit and human CAP18 peptides by in silico methods. After synthesis of peptides, the antimicrobial properties and LPS-binding activity of these peptides were evaluated. The parental rabbit and human CAP18 peptides were selected as positive controls. Next, the changes in the secondary structure of these peptides before and after treatment with LPS were measured by circular dichroism (CD). Human cytotoxicity of the peptides was evaluated by MTT and red blood cells (RBCs) hemolysis assays. Finally, field emission scanning electron microscopy (FE-SEM), confocal microscopy, and flow cytometry were performed to study the action mechanism of these peptides. Results indicated that the hCap18 and rCap18 had antibacterial activity (at a MIC of 4–128 μg/mL). The results of the quantitative LAL test demonstrated that LPS-binding activity of hCap18 peptide was better than rCap18, while rCap18 peptide had better antimicrobial properties. Furthermore, rCap18 had less cytotoxicity than hCap18. However, both peptides were nontoxic for normal human skin fibroblast cell in MIC range. In conclusion, rCap18 has good antibacterial properties, while hCap18 can be tested as a diagnostic molecule in our future studies. Keywords Antimicrobial peptides . Lipopolysaccharide . Cap18 . LPS-binding peptide . In silico drug design
Introduction Septic shock arises from a cascade of molecular and cellular events following infection by microorganisms, predominantly Hamid Madanchi and Ramin Ebrahimi Kiasari are co-first authors and contributed equally to this research * Soroush Sardari [email protected] Hamid Madanchi [email protected] 1
Department of Biotechnology, School of Medicine, Semnan University of Medical Sciences, Semnan, Iran
2
Drug Design and Bioinformatics Unit, Medical Biotechnology Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran
3
Department of Medical Biotechnology, School of Medicine, Zanjan University of Medical Sciences, Zanjan, Iran
Gram-negative bacteria [1]. Lipopolysaccharide (LPS) is the main cause of Gram-negative bacterial sepsis [2]. LPS consists of a lipid A component, a sugar moiety forming the core, and an O-polysaccharide of variable length [3]. In addition, LPS is one of the pyogenic agents in biological pharmaceutical
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