Extended Data Fig. 1: Cholesterol binding primarily drives renal toxicity of AmB, not ion channel formation.
From: Tuning sterol extraction kinetics yields a renal-sparing polyene antifungal
a, Synthesis of C35MeOAmB, a non-ion-channel forming antifungal probe starting from AmB. b, C35MeOAmB binds cholesterol during UV-Vis binding assay. c, C35MeOAmB does not permeabilize human red blood cells. Pre-complexation with cholesterol mitigates renal toxicity of both d, AmB and e, C35MeOAmB against human primary renal cells. Cholesterol (53 mg/g) in β-Me cyclodextrin (MβCD) obtained from Sigma Aldrich (C495; Lot no SLCJ3255). Results are means ± SD (n = 3 biological replicates/time point). In d, all pairwise comparisons with corresponding (1:0) at each concentration were performed using two-way ANOVA with Tukey’s multiple comparison test; *P = 0.028, **P = 0.0086, **P = 0.0019, ***P = 0.0004, ***P = 0.0003, ****P < 0.0001. In e, all pairwise comparisons with corresponding (1:0) at each concentration were performed using two-way ANOVA with Tukey’s multiple comparison test; ***P = 0.0004, ****P < 0.0001.
