Human lectins are critical carbohydrate-binding proteins that recognize diverse glycoconjugates from microorganisms and can play a key role in host-microbe interactions. Despite their importance in immune recognition and pathogen binding, the specific glycan ligands and functions of many human lectins remain poorly understood. Using previous proof-of-concept studies on selected lectins as the foundation for this work, we present ten additional glycan analysis probes (GAPs) from a diverse set of human soluble lectins, offering robust tools to investigate glycan-mediated interactions.
View Article and Find Full Text PDFGlycan-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.
View Article and Find Full Text PDFBackground: 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.
View Article and Find Full Text PDFLoss-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.
View Article and Find Full Text PDFBackground: Recent studies suggest discrepancies between patients and providers around perceptions of hemodialysis prognosis. Such data are lacking for continuous renal replacement therapy (CRRT). We aim to assess patient and provider understanding of outcomes around CRRT.
View Article and Find Full Text PDFA flow chemistry process for the Oppenauer oxidation of benzylic secondary alcohols using partially hydrated zirconium oxide and a simple carbonyl containing oxidant such as acetone, cyclohexanone, and neopentanal is reported. The heterogeneous oxidative system could be applied to a wide range of functionalized alcohol substrates, allowing clean and fast delivery of ketone products within a few minutes between 40 and 100 °C.
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