ArticleJournal of biomolecular NMR2020
Efficient affinity ranking of fluorinated ligands by
Article in Journal of biomolecular NMR, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 17 citations in OpenAlex.
- Parallelized 61-Sample Inhibition Screening Accelerated bySmall methods · 2026Article
- A ComprehensiveAngewandte Chemie (International ed. in English) · 2026Article
- High-Resolution Relaxometry for Fragment Screening.Journal of medicinal chemistry · 2026Article
- CSAKD: Determining Absolute Ligand Affinities FromAngewandte Chemie (International ed. in English) · 2026Article
- Quantitative Competition Binding of Fluorinated Ligands by Real-TimeMagnetic resonance in chemistry : MRC · 2026Article
- Article
- Quantification of Ligand-Membrane Interactions Using DNP-NMR Relaxometry.Analytical chemistry · 2026Article
- EstablishingAnalytical chemistry · 2026Article
- Target Engagement Assays in Early Drug Discovery.Journal of medicinal chemistry · 2025Review
- Perspectives on Applications ofMolecules (Basel, Switzerland) · 2024Review
- Micromolar fluoride contamination arising from glass NMR tubes and a simple solution for biomolecular applications.Journal of biomolecular NMR · 2024Article
- Practical Considerations and Guidelines for Spectral Referencing for Fluorine NMR Ligand Screening.ACS omega · 2022Article
- Review
- Article
- NMR in pharmaceutical discovery and development.Journal of biomolecular NMR · 2020Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Fluorine NMR has recently gained high popularity in drug discovery as it allows efficient and sensitive screening of large numbers of ligands. However, the positive hits found in screening must subsequently be ranked according to their affinity in order to prioritize them for follow-up chemistry. Unfortunately, the primary read-out from the screening experiments, namely the increased relaxation rate upon binding, is not proportional to the affinity of the ligand, as it is polluted by effects such as exchange broadening. Here we present the method CSAR (Chemical Shift-anisotropy-based Affinity Ranking) for reliable ranking of fluorinated ligands by NMR, without the need of isotope labeled protein, titrations or setting up a reporter format. Our strategy is to produce relaxation data that is directly proportional to the binding affinity. This is achieved by removing all other contributions to relaxation as follows: (i) exchange effects are efficiently suppressed by using high power spin lock pulses, (ii) dipolar relaxation effects are approximately subtracted by measuring at two different magnetic fields and (iii) differences in chemical shift anisotropy are normalized using calculated values. A similar ranking can be obtained with the simplified approach FastCSAR that relies on a measurement of a single relaxation experiment at high field (preferably > 600 MHz). An affinity ranking obtained in this simple way will enable prioritizing ligands and thus improve the efficiency of fragment-based drug design.
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