Protein drug screens

An excellent example of the use of isotope labeling in NMR spectroscopy is in its application to studies of protein structure and protein-ligand interaction. Such studies are of prime importance for drug screening and drug design. Consequently this field of research has been supported by drug companies. 

A number of indirect methods have been developed with mass spectrometric detection to rapidly study non-covalent complexes for drug screening purposes [2]. Among the most promising and simple indirect methods that overcome the limitations described above for directly studying non-covalent complexes by mass spectrometry is the application of size exclusion techniques in the spin column format for the screening and analysis of drug-protein complexes under optimum mass spectral sensitivity conditions [11-13]. 

Table 2.2 GPC spin column/ESI-MS drug screening high throughput aspects compounds assayed per day and protein consumed per compound. 

Fig. 2.11 An automatical generated drug screening ESI-MS report for the ESI background subtracted mass spectrum, illustrated in Fig. 2.1 OC, obtained from the GPC spin column eluate of the ten-component mixture incubated with RGS4 protein from well Al. Note that the highlighted components are the three compound hits that non-covalentl) bind to the RGS4 protein.

For example, to establish novel drug-screening system for small molecules based on protein-protein interactions using... 

TABLE 5.3 Results from an LC/MS-based drug-protein binding screen using HPLC columns containing immobilized human serum albumin to determine the relative binding of drugs... 

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