Design and Synthesis of New Cationic Antimicrobial Peptides with Low Cytotoxicity
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Design and Synthesis of New Cationic Antimicrobial Peptides with Low Cytotoxicity Pengbi Liu1,2 · Xiaomei Zeng2 · Xuejun Wen2 Accepted: 23 October 2020 © Springer Nature B.V. 2020
Abstract According to the mechanisms of antimicrobial peptides presented in current research literatures, four cationic peptides rich in arginine residues were designed and synthesized in this study. Their antimicrobial activity to four microorganisms and cytotoxicity to human dermal fibroblasts (HDFs) were evaluated. Among these peptides, PEP-1, PEP-2 and PEP-4 could inhibit and kill these microorganisms at certain concentrations. While PEP-3 only exhibited low inhibition activity against E. coli. PEP-1 rich in arginine residues was more effective against Gram-negative bacteria. PEP-4 with tryptophan and lysine residues in the sequence exhibited enhancement in the antimicrobial activity compared with PEP-3 and presented lowest minimal bactericidal concentration (MBC) to S. aureus and C. albicans in these four peptides. These results indicate that the amount and position of cationic residues in the sequence affects the bactericidal activity and the complement of proline with arginine, tryptophan with arginine and lysine residues would enhance the antimicrobial activity. Moreover, PEP-1, PEP-2 and PEP-4 showed low toxicity at their 1× MBC with no considerable difference with the negative control group in the HDFs cytotoxicity test. This study provides us with a better understanding on the structure-activity relationship, which will be useful for new antimicrobial peptide designs and optimizations. Keywords Antimicrobial peptides · Cytotoxicity · Arginine · Cationic peptides · Hydrophilic peptides
Introduction Natural antimicrobial peptides (AMPs) are secreted by innate immune system of various organisms. To date, more than 3000 AMPs are identified and documented in the AMP database, including some synthetic peptides (Wang et al. 2015). AMPs are deemed promising antimicrobial agents due to their broad-spectrum and efficient antimicrobial activities. Traditional antibiotics against pathogenic microorganism usually inhibit enzymes that are necessary for microbial growth or survival. However, many microbes have developed drug-resistance due to the widespread use * Pengbi Liu [email protected] * Xuejun Wen [email protected] 1
School of Textile Materials and Engineering, Wuyi University, Jiangmen 529020, Guangdong, China
Department of Chemical and Life Science Engineering, College of Engineering, Virginia Commonwealth University, Richmond, VA 23284, USA
2
of antibiotics. Unlike traditional antibiotics, AMPs primarily target and disrupt the microbial cell membrane (Nguyen et al. 2011; Yeaman and Yount 2003), suggesting that they may potentially escape the multidrug resistance mechanisms (Matsuzaki 2009). Many researchers have shown that AMPs are more efficient in inhibiting drug-resistant microbes compared with the traditional antimicrobial agents and kill bacteria more rapidly (Arfan et al. 2019; Hancock and Patrzykat 2002; Findlay et
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