Evaluation of l‐2,4‐diaminobutyric acid‐based ultrashort cationic lipopeptides as potential antimicrobial and anticancer agents

Abstract

Ultrashort cationic lipopeptides (USCLs) are amphiphiles that exhibit antimicrobial and anticancer activity. They are composed of an aliphatic chain attached to a positively charged peptide group consisting of a few amino acid residues. Here, we report the activity of a series of l‐2,4‐diaminobutyric acid (Dab)‐rich USCLs with varying N‐acyl chain length and charge against Escherichia coli, Staphylococcus aureus, Candida albicans, colon, breast, and lung epithelial cancer cell lines. USCLs with chain lengths of 14–18 carbons showed significant antimicrobial activity with C16‐conjugated peptides being the most active against E. coli and S. aureus, and C18‐conjugated peptides being the most active against C. albicans. Doubly charged USCLs with aliphatic tails that are 14 carbon atoms and longer showed more potent anticancer activity compared to their triply charged counterparts. C14‐Dab2‐NH2 displayed little toxicity to normal cells, and selectivity to microbial and cancer cells over normal cells. Its structural simplicity, bioactivity, nontoxicity, and selectivity make it a promising therapeutic agent.

Chimeric Peptidomimetic Antibiotic Efficiently Neutralizes Lipopolysaccharides (LPS) and Bacteria-Induced Activation of RAW Macrophages

“…20 Another microbial AMP, Nisin-A has also been reported to regulate apoptosis and T cell proliferation, in addition to LPS neutralization. 18 Polymyxin B nonapeptide (PMBN) (Figure 1B), a cyclic peptide obtained from enzymatic processing of PMB, is capable of binding to LPS, rendering Gram-negative bacteria susceptible to antimicrobials 21 and has also been shown to reduce LPS-triggered inflammatory markers, 22 suggesting a similar immunomodulatory potential as PMB. These studies suggest a potential dual role for natural and synthetic peptides as direct killing and immunomodulatory therapeutic agents in cases of infections and sepsis.…”