Products Cited in Publications Worldwide Mimicking Charged Host-Defense Peptides to Tune the Antifungal Activity and Biocompatibility of Amphiphilic Polymers

Mimicking Charged Host-Defense Peptides to Tune the Antifungal Activity and Biocompatibility of Amphiphilic Polymers

Sebastian Schaefer; Daniele Melodia; Christopher Pracey; Nathaniel Corrigan; Megan D. Lenardon; Cyrille Boye

DOI:

Abstract

Invasive fungal infections impose a substantial global health burden. They cause more than 1.5 million deaths annually and are insufficiently met by the currently approved drugs. are a promising alternative to existing drugs; however, they can be challenging to synthesize, and are often susceptible to proteases in vivo. Synthetic which mimic the properties of natural can circumvent these limitations. In this study, we developed a library of 29 amphiphilic polyacrylamides with different charged units, namely, , guanidinium, , and groups, representative of the natural lysine, arginine, , and . Ternary polymers incorporating primary ammonium (lysine-like) or (histidine-like) groups demonstrated superior activity against Candida albicans and biocompatibility with mammalian cells compared to the containing the other charged groups. Furthermore, a combination of primary ammonium, , and guanidinium (arginine-like) within the same polymer outperformed the drug in terms of therapeutic index and exhibited fast C. albicans-killing activity. The most promising polymer compositions showed synergistic effects in combination with caspofungin and against C. albicans and additionally demonstrated activity against other clinically relevant fungi. Collectively, these results indicate the strong potential of these easily producible polymers to be used as .

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