← Library
JACSJournal of the American Chemical Society
2023 · Vol. 145 · No. 22pp. 12066–12080
Article
Ultrafast Fragment Screening Using Photo-Hyperpolarized (CIDNP) NMR
Felix Torres, Matthias Bütikofer, Gabriela R. Stadler, Alois Renn, Harindranath Kadavath, Raitis Bobrovs, Kristaps Jaudzems, Roland Riek
| Journal | J. Am. Chem. Soc. 2023, 145 (22), 12066–12080 |
| DOI | 10.1021/jacs.3c01392 |
| Filed under | Drug discovery › Screening |
Summary
NMR is a reference method for fragment-based drug design. Its low sensitivity means long acquisitions and high sample concentrations. This paper uses photo-CIDNP to remove both limits.
Binding is read from the loss of the ligand signal when the target is present, because only the free ligand is polarised. Weak binders in the millimolar affinity range were detected with 5 µM of ligand and 2 µM of target, in single-scan experiments of 2 to 5 s.
An automated flow-through platform reached 1,500 samples per day. The paper also presents a library of 212 photo-CIDNP-active fragments.
Key figures
- Scan
- 2 to 5 s, single
- Ligand
- 5 µM
- Target
- 2 µM
- Throughput
- 1,500 samples per day
- Library
- 212 fragments
Related
Chemistry Methods2024
ArticleRescaling NMR for a Larger Deployment in Drug Discovery: Hyperpolarization and Benchtop NMR as Potential Game-ChangersBütikofer, Stadler, Torres. Chemistry Methods 2024, 4, e202400009
JACS2024
Article · Affinity determinationRapid Protein–Ligand Affinity Determination by Photoinduced Hyperpolarized NMRBütikofer, Stadler, Kadavath, Cadalbert, Torres, Riek. J. Am. Chem. Soc. 2024, 146, 17974–17985
Magritek2024
Application noteLet your NMR signal shine – Automated photoCIDNP experiments with a Spinsolve benchtop NMRMagritek, 1 March 2024
ApplicationFragment screeningFind which fragments of a library bind a target, from one photo-CIDNP scan per sample.