Effective antimicrobial activity of a peptide mutant Cbf-14-2 against penicillin-resistant bacteria based on its unnatural amino acids

European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences
Wei KangJie Dou

Abstract

Broad spectrum activities, a unique mode of actions and rare resistant variants make antimicrobial peptide (AMP) a potential alternative to antibiotics. However, AMPs still have limitations in clinical development due to their physiological stability, toxicity and manufacturing costs. Cbf-14, derived from cathelicidin-BF has been proven to be effective against drug-resistant bacteria. Herein, a series of Cbf-14 mutants were designed to overcome these limitations. Design strategies included substitutions of lysine (Lys) or leucine (Leu) with similar residues such as ornithine (Orn) and norleucine (Ile), which are unnatural amino acids, to generate AMPs with enhanced therapeutic potential. Antimicrobial activity, hemolytic activity and cytotoxicity against mouse spleen cells of the peptide mutants were investigated. Among all of the mutants, Cbf-14-2 was regarded as the most potent candidate with the amino acid sequence of RLLR-Orn-FFR-Orn-LKKSV-NH2, which exhibited a superior antimicrobial activity with a minimum inhibitory concentration (MIC) of 4-32μg/ml. Meanwhile, Cbf-14-2 displayed low levels of hemolysis in sheep red blood cells (sRBCs) and negligible cytotoxicity against mouse spleen cells, suggesting low toxicity against...Continue Reading

Citations

Nov 2, 2018·Yakugaku zasshi : Journal of the Pharmaceutical Society of Japan·Tsubasa Inokuma
Jan 25, 2020·Biochimie·Sathishkumar MunusamyCarlos Munoz-Garay
Jul 6, 2021·Frontiers in Chemistry·Tanumoy SarkarSunanda Chatterjee

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