title: Structure-activity relationships among antifungal nylon-3 polymers: identification of materials active against drug-resistant strains of Candida albicans.
abstract: Fungal infections are a major challenge to human health that is heightened by pathogen resistance to current therapeutic agents. Previously, we were inspired by host-defense peptides to develop nylon-3 polymers (poly-β-peptides) that are toxic toward the fungal pathogen Candida albicans but exert little effect on mammalian cells. Based on subsequent analysis of structure-activity relationships among antifungal nylon-3 polymers, we have now identified readily prepared cationic homopolymers active against strains of C. albicans that are resistant to the antifungal drugs fluconazole and amphotericin B. These nylon-3 polymers are nonhemolytic. In addition, we have identified cationic-hydrophobic copolymers that are highly active against a second fungal pathogen, Cryptococcus neoformans, and moderately active against a third pathogen, Aspergillus fumigatus.
authors.affiliation: Department of Chemistry, ‡Department of Biomedical Engineering, §Department of Medicine, and ∥Department of Chemical and Biological Engineering, University of Wisconsin , Madison, Wisconsin 53706, United States.
authors.forename: Runhui
authors.initials: R
authors.lastname: Liu
authors.forename: Xinyu
authors.initials: X
authors.lastname: Chen
authors.forename: Shaun P
authors.initials: SP
authors.lastname: Falk
authors.forename: Brendan P
authors.initials: BP
authors.lastname: Mowery
authors.forename: Amy J
authors.initials: AJ
authors.lastname: Karlsson
authors.forename: Bernard
authors.initials: B
authors.lastname: Weisblum
authors.forename: Sean P
authors.initials: SP
authors.lastname: Palecek
authors.forename: Kristyn S
authors.initials: KS
authors.lastname: Masters
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Gellman
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002176:Candida albicans / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D025141:Drug Resistance, Fungal / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009757:Nylons / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000935:Antifungal Agents; D009757:Nylons