Sensitivity enhancement in saturation transfer difference (STD) experiments through optimized excitation schemes |
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Authors: | Cutting Brian Shelke Sachin V Dragic Zorica Wagner Beatrice Gathje Heiko Kelm Soerge Ernst Beat |
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Affiliation: | University of Basel, Institute of Molecular Pharmacy, Klingelbergstrasse 50, CH-4056 Basel, Switzerland. brian.cutting@unibas.ch |
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Abstract: | Investigation of ligand-protein interactions by the saturation transfer difference (STD) experiment has been well established in the drug discovery process through numerous examples. Thus, binding epitopes may be mapped by comparing signals of the ligand with and without saturation of the protein. Herein, it is shown that a less selective process allows more protons to assist in the saturation of the protein, thereby considerably enhancing the sensitivity of the STD experiment. Increasing the saturation power entails a greater risk of perturbing the ligand; however, an amplitude modulation of the waveform assists this procedure by distributing the applied energy in sidebands. |
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Keywords: | NMR 1H saturation transfer difference (STD) screening epitope mapping spin diffusion |
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