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An NMR study to examine the binding of solvent molecules to lysozyme; the solution equivalent of the MSCS technique for crystal structures [9,10]. Results indicate that most solvent molecules found to occupy protein sites in the crystal do not bind to high affinity sites, but rather bind weakly to sites formed due to crystal packing. NMR methods detect only the higher affinity ligand molecules, and do not suffer from the artificial occupancy problems of MSCS.
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Liepinsh E, Otting G Organic solvents identify specific ligand binding sites on protein surfaces. Nat Biotechnol. 15:1997;264-268. An NMR study to examine the binding of solvent molecules to lysozyme; the solution equivalent of the MSCS technique for crystal structures [9,10]. Results indicate that most solvent molecules found to occupy protein sites in the crystal do not bind to high affinity sites, but rather bind weakly to sites formed due to crystal packing. NMR methods detect only the higher affinity ligand molecules, and do not suffer from the artificial occupancy problems of MSCS.
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Application of the SAR by NMR method to design two potent (<25 nM) inhibitors of stromelysin. This work provides a step by step description of the design protocol and is an excellent source of information for scientists working directly in the field.
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••], the design protocol is described in detail. This work is of special importance because lead compounds were obtained for a target for which little chemistry was known.
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An excellent example of how the transferred NOE experiment may be used to screen libraries of small molecules against a protein target. In this paper, two mixtures of oligosaccharides were screened against Aleuria aurantia agglutinin. From the 2D spectra, a single binding ligand from each mixture could be readily identified and characterized.
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A practical description of how NMR relaxation and diffusion difference methods, well known techniques for the study of macromolecule/small molecule interactions, may be used to screen large libraries of small molecules against a macromolecular target.
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Hajduk PJ, Olejniczak ET, Fesik SW One-dimensional relaxation- and diffusion-edited NMR methods for screening compounds that bind to macromolecules. J Am Chem Soc. 119:1997;12257-12261. A practical description of how NMR relaxation and diffusion difference methods, well known techniques for the study of macromolecule/small molecule interactions, may be used to screen large libraries of small molecules against a macromolecular target.
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