Micromolar concentration affinity study on a benchtop NMR spectrometer with secondary ¹³C labeled hyperpolarized ligands
Author(s)
Type
Journal Article
Abstract
Benchtop NMR is becoming an increasingly important tool, sometimes providing a simple and low-cost alternative to high-field NMR. The Achilles heel of NMR and even more critically of benchtop NMR is its limited sensitivity. However, when combined with hyperpolarization techniques, the sensitivity boost can provide excellent sensitivity that can even make benchtop NMR compatible with affinity studies for drug discovery. Hyperpolarization by dissolution dynamic nuclear polarization (dDNP) provides a route to enhancing 13C nuclear magnetic resonance (NMR) sensitivity by more than 5 orders of magnitude for a wide range of small molecules on a benchtop NMR system. We show here how ligands can be secondarily labeled with 13C tags and hyperpolarized with conventional dDNP methods. These hyperpolarized ligands display long nuclear spin–lattice relaxation time constants and can therefore be used to probe interactions with target proteins in conventional dDNP settings. The boost in sensitivity combined with the simplicity of the 13C spectra (one peak per ligand) enables detection on an 80 MHz benchtop NMR spectrometer at micromolar concentrations, which may ultimately provide a way of improving and accelerating the discovery of new drug candidates.
Date Issued
2025-02-04
Date Acceptance
2025-01-17
Citation
ACS Omega, 2025, 10 (4), pp.3332-3337
ISSN
2470-1343
Publisher
American Chemical Society
Start Page
3332
End Page
3337
Journal / Book Title
ACS Omega
Volume
10
Issue
4
Copyright Statement
© 2025 The Authors. Published by American Chemical Society. This publication is licensed under CC-BY-NC-ND 4.0 .
Publication Status
Published
Date Publish Online
2025-01-24