Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5407595 | Journal of Magnetic Resonance | 2006 | 11 Pages |
Abstract
NMR based ligand screening is becoming increasingly important for the very early stages of drug discovery. We have proposed a method that makes highly efficient use of a single sample of a scarce target, or one with poor or limited solubility, to screen an entire compound library. This comparative method is based on immobilizing the target for the screening procedure. In order to support the method, a dual cell, flow injection probe with a single receiver coil has been constructed. The flow injection probe has been mated to a single high performance pump and sample handling system to enable the automated analysis of large numbers of compound mixes for binding to the target. The probe, having an 8Â mm 1H/2H dual tuned coil and triple axis gradients, is easily shimmed and yields NMR spectra of comparable quality to a standard 5Â mm high-resolution probe. The lineshape in the presence of a solid support is identical to that in glass NMR tubes in a 5Â mm probe. Control spectra of each cell are identical and well separated, while ligand binding in a complex mixture can be readily detected in 20-30Â min, thus paving the way for use of the probe for actual drug discovery efforts.
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Authors
Thorsten Marquardsen, Martin Hofmann, Johan G. Hollander, Caroline M.P. Loch, Suzanne R. Kiihne, Frank Engelke, Gregg Siegal,