NMR screening methods

NMR screening methods can detect very weak binders, which shifts the measurable inhibition curve (Fig. 18.6) toward less complex molecules. So, it is theoretically more... 

The cryo-LC probe offers an enhancement of np to four-fold in sensitivity over conventional LC probes. Hyphenated techniques such as LC-NMR and LC-SPE-NMR, as well as high-thronghput NMR screening methods, will benefit from this significant increase in sensitivity. 

Table I Advantages and disadvantages of target- and ligand-based NMR screening methods...

Tian C, Karra MD, Ellis CD, Jacob J, Oxenoid K, Sonnichsen F, Sanders CR (2005) Membrane protein preparation for TROSY NMR screening. Methods Enzymol 394 321-334... 

R. Consonni and M. Veronesi, NMR Screening Methods in Fragment-Based Drug Discovery, in Structure - Activity Relationship Studies in Drug Development by NMR Spectroscopy, ed. Atta-ur-Rahman and M. I. Choudhaiy, Bentham Seienee Publishers Ltd., 2011, vol. 1 p. 67. 

Fig. 1.10 Cdk2 inhibitor identified using NMR screening by the WaterLOGSY method.

Center is unique across the network in having the capability to perform NMR-based small-molecule screening and optimization. NMR-based methods are exceptionally valuable when investigating molecular targets that are not easily tractable by other methods, such as protein-protein interactions and protein targets that cannot be formatted for the classical HTS environment. 

This review focuses upon NMR screening strategies and discusses how compound libraries can be designed to provide information pertinent to the specific strategy being pursued. The principles and tools of library construction are described and illustrated by the example of the approach used in our laboratory. The technical details of experimental methods will not be discussed here since they are reviewed in other chapters of this volume and elsewhere [1],... 

Dissimilarity and clustering methods only describe the compounds that are in the input set voids in diversity space are not obvious, and if compounds are added then the set must be re-analyzed. Cell-based partitioning methods address these problems by dividing descriptor space into cells, and then populating those cells with compounds [67, 68]. The library is chosen to contain representatives from each cell. The use of a partition-based method with BCUT descriptors [69] to design an NMR screening library has recently been described [70]. 

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