Multi-Selective One Dimensional Proton NMR Experiments for Rapid Screening and Binding Affinity Measurements

Title: Multi-Selective One Dimensional Proton NMR Experiments for Rapid Screening and Binding Affinity Measurements

Volume: 6 Issue: 5

Author(s): Claudio Dalvit, Daneen T.A. Hadden, Ronald W. Sarver, Andrea M. Ho and Brian J. Stockman

Affiliation:

Keywords: high throughput screening, dissociation binding constant, competition binding experiments, drug discovery, multi-selective nmr experiments, human serum albumin

Abstract: High-throughput ligand-based proton NMR screening performed in the presence of a spy molecule and a control molecule is a valuable tool for identifying drug leads. A limitation of the technique is represented by the severe overlap encountered in the screening of large chemical mixtures. An approach for overcoming this overlap problem is the use of multi-selective R1 filtered and COSY or TOCSY experiments. Application of this methodology to compounds binding to the Sudlow site I of human serum albumin is presented. The screening is performed by simply monitoring the intensity of two signals. The precise measurement of the relative intensity of the two resonances permits determination of the binding constant of the NMR-hit. For a simple competition binding mechanism, the rapidly-derived NMR binding constants are in good agreement with the values derived from full-titration ITC and fluorescence spectroscopy measurements.

Cite this article as:

Dalvit Claudio, Hadden T.A. Daneen, Sarver W. Ronald, Ho M. Andrea and Stockman J. Brian, Multi-Selective One Dimensional Proton NMR Experiments for Rapid Screening and Binding Affinity Measurements, Combinatorial Chemistry & High Throughput Screening 2003; 6 (5) . https://dx.doi.org/10.2174/138620703106298626