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We previously developed amine\u2010pendent poly(2\u2010oxazoline)s (POXs) as synthetic mimics of host defense peptides (HDPs) to have antibacterial properties, but with poor antifungal activity. Hereby, we report the finding of short guanidinium\u2010pendent POXs, inspired by cell\u2010penetrating peptides, as synthetic mimics of HDPs to display potent antifungal activity, superior mammalian cells versus fungi selectivity, and strong therapeutic efficacy in treating local and systemic fungal infections. Moreover, the unique antifungal mechanism of fungal cell membrane penetration and organelle disruption explains the insusceptibility of POXs to antifungal resistance. The easy synthesis and structural diversity of POXs imply their potential as a class of promising antifungal agents.<\/jats:p>","DOI":"10.1002\/anie.202200778","type":"journal-article","created":{"date-parts":[[2022,2,19]],"date-time":"2022-02-19T07:23:09Z","timestamp":1645255389000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":78,"title":["Short Guanidinium\u2010Functionalized Poly(2\u2010oxazoline)s Displaying Potent Therapeutic Efficacy on Drug\u2010Resistant Fungal Infections"],"prefix":"10.1002","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5393-5713","authenticated-orcid":false,"given":"Weinan","family":"Jiang","sequence":"first","affiliation":[{"name":"State Key Laboratory of Bioreactor Engineering East China University of Science and Technology  Shanghai 200237 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