Work

Affinity Screening Using Competitive Binding with Fluorine‐19 Hyperpolarized Ligands

Year: 2015

Type: article

Abstract: Fluorine-19 NMR and hyperpolarization form a powerful combination for drug screening. Under a competitive equilibrium with a selected fluorinated reporter ligand, the dissociation constant (K(D)) of other ligands of interest is measurable using a single-scan Carr-Purcell-Meiboom-Gill (CPMG) experiment, without the need for a titration. This method is demonstrated by characterizing the binding of three ligands with different affinities for the serine protease trypsin. Monte Carlo simulations show that the highest accuracy is obtained when about one-half of the bound reporter ligand is displaced in the binding competition. Such conditions can be achieved over a wide range of affinities, allowing for rapid screening of non-fluorinated compounds when a single fluorinated ligand for the binding pocket of interest is known.

Source: Angewandte Chemie International Edition

DOI: 10.1002/anie.201411424

Authors: Yaewon Kim, Christian Hilty

Institution: Texas A&M University

Language: English

Topic: Advanced NMR Techniques and Applications

Subfield: Spectroscopy

Field: Chemistry

Domain: Physical Sciences

Open Access status: green

Funders: National Institutes of Health, National Institute of General Medical Sciences

Awards: G1737273289, Development of Platform for Ligand Screening using Hyperpolarized NMR, G8889236041, G9000341316