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Updated: May 7, 2026

NMR-Based Fragment Screening in a Minimum Sample but Maximum Automation Mode
Published on: June 4, 2021
19F NMR Functional Screening on a Benchtop NMR Instrument: Theoretical Analysis and Efficient Application to Drug
Christina Jordan1, Martial Piotto2, Sandra Loss3
1Institute of Biochemistry, Department of Biology, ETH Zürich, Hönggerbergring 64, CH-8093 Zürich, Switzerland.
Abstract:
Benchtop NMR instruments carry the potential to popularize and spread otherwise expensive NMR analyses, including applications in drug discovery. The main shortcoming of these affordable instruments is their limited sensitivity and resolution. Here, a functional assay based on 19F NMR on a commercial 80 MHz spectrometer is presented that reliably allows to determine the relative affinity of inhibitors over a large range of potency. An assay on the cancer-related enzyme thymidine phosphorylase was set up, and IC50 values for different inhibitors covering the range from nM to hundreds of μM were determined. The limitations and strengths of this n-FABS assay are evaluated theoretically in depth. Based on these insights, optimized assays with fluorinated substrates can be implemented, which provide an ideal opportunity for efficient and cost-effective functional assays on benchtop NMR instruments.
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