Molecular prosthetics for CFTR designed for anion selectivity outperform amphotericin B in cultured cystic fibrosis airway epithelia.

ABSTRACT: The ion channel-forming natural product amphotericin B (AmB) can serve as a molecular prosthetic for the cystic fibrosis transmembrane conductance regulator (CFTR) anion channel and thereby restore host defenses in cultured cystic fibrosis (CF) airway epithelia. This is despite the fact that the permeability of AmB-based channels favors cations, and these channels lose their capacity to increase airway surface liquid (ASL) pH in CF airway epithelia at high concentrations. We hypothesize that modifying such channels to favor anion permeability would make them more CFTR-like and thus increase their potential therapeutic effects compared to AmB. Here we show that a synthetic derivative of AmB, AmB-AA, which has an added positively charged appendage and forms ion channels with an improved rela

SUBMITTER: Marin-Toledo JP 

PROVIDER: S-EPMC12407901 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature