Abstract
The link between the antimicrobial and anticancer activity of peptides has long been studied, and the number of peptides identified with both activities has recently increased considerably. In this work, we hypothesized that designed peptides with a wide spectrum of selective antimicrobial activity will also have anticancer activity, and tested this hypothesis with newly designed peptides. The spectrum of peptides, used as partial or full design templates, ranged from cell-penetrating peptides and putative bacteriocin to those from the simplest animals (placozoans) and the Chordata phylum (anurans). We applied custom computational tools to predict amino acid substitutions, conferring the increased product of bacteriostatic activity and selectivity. Experiments confirmed that better overall performance was achieved with respect to that of initial templates. Nine of our synthesized helical peptides had excellent bactericidal activity against both standard and multidrug-resistant bacteria. These peptides were then compared to a known anticancer peptide polybia-MP1, for their ability to kill prostate cancer cells and dermal primary fibroblasts. The therapeutic index was higher for seven of our peptides, and anticancer activity stronger for all of them. In conclusion, the peptides that we designed for selective antimicrobial activity also have promising potential for anticancer applications.
Highlights
Antimicrobial peptides (AMPs) are small (5–50 amino acid residues), mostly cationic and amphipathic molecules, often associated with a broad activity spectrum against different cell types [1,2,3,4].As host defense peptides (HDPs), they occur naturally as part of the innate immune defense, for instance, in multicellular organisms [5]
The selectivity index is calculated as selectivity index abbreviation (SI) (20) = HC20 /minimal inhibitory concentration (MIC) or SI (50) = HC50 /MIC
The peptides presented in this work offer a wide spectrum of novel helical structures as lead compounds for fine-tuning their anticancer potential
Summary
Antimicrobial peptides (AMPs) are small (5–50 amino acid residues), mostly cationic and amphipathic molecules, often associated with a broad activity spectrum against different cell types [1,2,3,4]. As host defense peptides (HDPs), they occur naturally as part of the innate immune defense, for instance, in multicellular organisms [5]. Such peptides are easy to synthesize, with a general mechanism of membrane-perturbing activity. The main design challenge in this research field is to simultaneously achieve the goals of wide-spectrum antimicrobial activity and low toxicity to human cells. Activity against multidrug-resistant bacteria is a highly worthwhile goal
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