CH-π Interactions Are Required for Human Galectin-3 Function.

Glycan-binding proteins, or lectins, recognize distinct structural elements of polysaccharides, to mediate myriad biological functions. Targeting glycan-binding proteins involved in human disease has been challenging due to an incomplete understanding of the molecular mechanisms that govern protein-glycan interactions. Bioinformatics and structural studies of glycan-binding proteins indicate that aromatic residues with the potential for CH-π interactions are prevalent in glycan-binding sites.

Amphotericin B induces epithelial voltage responses in people with cystic fibrosis.

Background: Approximately 10% of people with cystic fibrosis (CF) have mutations that result in little to no CFTR production and thus cannot benefit from CFTR modulators. We previously found that Amphotericin B (AmB), a small molecule that forms anion channels, restored HCO secretion and increased host defenses in primary cultures of CF airway epithelia. Further, AmB increased ASL pH in CFTR-null pigs, suggesting an alternative CFTR-independent approach to achieve gain-of-function.

Small-molecule ion channels increase host defences in cystic fibrosis airway epithelia.

Loss-of-function mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) compromise epithelial HCO and Cl secretion, reduce airway surface liquid pH, and impair respiratory host defences in people with cystic fibrosis. Here we report that apical addition of amphotericin B, a small molecule that forms unselective ion channels, restored HCO secretion and increased airway surface liquid pH in cultured airway epithelia from people with cystic fibrosis. These effects required the basolateral Na, K-ATPase, indicating that apical amphotericin B channels functionally interfaced with this driver of anion secretion.