Protein‐free ligand screening: simplification of chiral chromatographic development via novel adaptation of NMR screening methodologies

Abstract

We demonstrate here a promising NMR method that provides evidence for chiral compound selector interaction as a first-pass screening method. A novel adaptation of commonly used protein-based screening technologies, this approach relies upon ligand-to-stationary phase interaction wherein the stationary phase is tethered to sepharose beads. At only minutes per experiment, this methodology significantly reduces the time required for chiral separation methodology development and complements currently available chromatographic purity technologies.

NMR Spectroscopy for Studying Interactions of Bioactive Molecules

“…Those findings demonstrated the specificity of anaesthetics for a particular protein conformation. Several research groups have proposed the implementation of STD-NMR spectroscopy in chromatographic optimisation studies [74,75]. STD-NMR in combination with molecular dynamics simulations can be used to screen chiral stationary phases for evidence of molecular interactions as a predictor of chiral column selection and to study the mechanism of chemically selective displacement chromatography.…”