Screening Protein-Ligand Interactions

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. 

It is important to note that the same ALIS hardware and software used for combinatorial library screening is applicable to characterizing protein-ligand interactions using the methods described below. 

Next to the detection of enzyme inhibition, ESI-MS can also be used to monitor protein-ligand interaction, employing an assay format similar to fluorescence-based receptor assays. Using a similar continuous-flow analytical screening system as shown in Fig. 5.2, a competitive assay can be set up using ESI-MS to measure the interaction of the analyte(s) with an affinity protein such as an antibody, receptor or enzyme [28]. Figure 5.10 shows the equilibrium reactions that form the basis of the assay concept. In a first step, the sample was injected into a con-... 

X is known, information about binding location. This can be exploited to direct the screen to a particular site on a protein. This location is typically the active site, but the method can also be used to investigate allosteric sites or protein-protein binding interfaces. In the following, we will describe various practical approaches to covalent capture and provide examples of their application in studying protein-ligand interactions and drug discovery. 

Small molecule screening on chemical microarrays. In Bohm, H.J., and Schneider, G. (eds.) Protein-Ligand Interactions, From Molecular Recognition to Drug Design. Wiley-VCH, Weinheim, pp. 213-236. 

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