Fluorine-NMR Competition Binding Experiments for High-Throughput Screening of Large Compound Mixtures

Title: Fluorine-NMR Competition Binding Experiments for High-Throughput Screening of Large Compound Mixtures

Volume: 5 Issue: 8

Author(s): Claudio Dalvit, Maria Flocco, Marina Veronesi and Brian J. Stockman

Affiliation:

Keywords: ligand-based NMR screening, High-Throughput Screening, dissociation binding constant, F NMR spectroscopy, competition binding experiments, drug discovery

Abstract: High-throughput ligand-based NMR screening with competition binding experiments is extended to 19F detection. Fluorine is a favorable nucleus for these experiments because of the significant contribution of the Chemical Shift Anisotropy (CSA) to the 19F transverse relaxation of the ligand signal when bound to a macromolecular target. A low to moderate affinity ligand containing a fluorine atom is used as a reference molecule for the detection and characterization of new ligands. Titration NMR experiments with the selected reference compound are performed for finding the optimal set-up conditions for HTS and for deriving the binding constants of the identified NMR hits. Rapid HTS of large chemical mixtures and plant or fungi extracts against the receptor of interest is possible due to the high sensitivity of the 19F nucleus and the absence of overlap with the signals of the mixtures to be screened. Finally, a novel approach for HTS using a reference molecule in combination with a control molecule is presented.

Cite this article as:

Claudio Dalvit , Maria Flocco , Marina Veronesi and Brian J. Stockman , Fluorine-NMR Competition Binding Experiments for High-Throughput Screening of Large Compound Mixtures, Combinatorial Chemistry & High Throughput Screening 2002; 5 (8) . https://dx.doi.org/10.2174/1386207023329923

DOI https://dx.doi.org/10.2174/1386207023329923	Print ISSN 1386-2073
Publisher Name Bentham Science Publisher	Online ISSN 1875-5402