Development of novel membrane active lipidated peptidomimetics active against drug resistant clinical isolates |
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| Affiliation: | 1. Molecular and Structural Biology Division, CSIR-Central Drug Research Institute, Lucknow 226031, India;2. Academy of Scientific and Innovative Research, New Delhi 110025, India;3. Centre of Biomedical Research (CBMR), Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Raibareli Road, Lucknow, Uttar Pradesh 226014, India;1. Programa de Pós-Graduação em Inovação Terapêutica, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil;2. Departamento de Bioquímica, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil;3. Centro de Análise Proteômicas e Bioquímicas de Brasília, Universidade Católica de Brasília, Brasília, DF, Brazil;4. Departamento de Física, Universidade Federal de Pernambuco, 50670-901 Recife, PE, Brazil |
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| Abstract: | A new series of small cationic lipidated peptidomimetics have been synthesized and found to be highly active against several susceptible as well as drug resistant clinical isolates of bacteria and fungi. All lipidated peptidomimetics do not cause significant lysis of human erythrocytes (HC50 > 200 μg/mL). Calcein dye leakage experiment revealed membranolytic effect of LPEP08 which was further confirmed by scanning electron microscopy (SEM). The involvement of intracellular targets as an alternate mode of action was precluded by DNA retardation assay. Additionally, LPEP08 exhibit high proteolytic stability and dose not elicit resistance against drug resistant clinical isolate of Staphylococcus aureus, even after 16 rounds of passaging. These results demonstrate the potential of lipidated peptidomimetics as biocompatible anti-infective therapeutics. |
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| Keywords: | Peptidomimetics Antimicrobial peptides Lipopeptides Drug resistance Membranolytic |
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