Synthesis-enabled functional group deletions reveal key underpinnings of amphotericin B ion channel and antifungal activities.

ABSTRACT: Amphotericin B is the archetype for small molecules that form transmembrane ion channels. However, despite extensive study for more than five decades, even the most basic features of this channel structure and its contributions to the antifungal activities of this natural product have remained unclear. We herein report that a powerful series of functional group-deficient probes have revealed many key underpinnings of the ion channel and antifungal activities of amphotericin B. Specifically, in stark contrast to two leading models, polar interactions between mycosamine and carboxylic acid appendages on neighboring amphotericin B molecules are not required for ion channel formation, nor are these functional groups required for binding to phospholipid bilayers. Alternatively, consistent with

SUBMITTER: Palacios DS 

PROVIDER: S-EPMC3084054 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature