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Improved potency and reduced toxicity of the antifungal peptoid AEC5 through submonomer modification.

ABSTRACT: As proteolytically stable peptidomimetics, peptoids could serve as antifungal agents to supplement a therapeutic field wrought with toxicity issues. We report the improvement of an antifungal peptoid, AEC5, through an iterative structure-activity relationship study. A sarcosine scan was used to first identify the most pharmacophorically important peptoid building blocks of AEC5, followed by sequential optimization of each building block. The optimized antifungal peptoid from this study, β-5, has improved potency towards Cryptococcus neoformans and decreased toxicity towards mammalian cells. For example, the selectivity ratio for C. neoformans over mammalian fibroblasts was improved from 8 for AEC5 to 37 for β-5.

SUBMITTER: Middleton MP

PROVIDER: S-EPMC6246776 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Improved potency and reduced toxicity of the antifungal peptoid AEC5 through submonomer modification.

Middleton Madyson P MP Armstrong Scott A SA Bicker Kevin L KL

Bioorganic & medicinal chemistry letters 20181003 22

As proteolytically stable peptidomimetics, peptoids could serve as antifungal agents to supplement a therapeutic field wrought with toxicity issues. We report the improvement of an antifungal peptoid, AEC5, through an iterative structure-activity relationship study. A sarcosine scan was used to first identify the most pharmacophorically important peptoid building blocks of AEC5, followed by sequential optimization of each building block. The optimized antifungal peptoid from this study, β-5, has ...[more]

PMID: 30297282

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