The Application of Label-free Technologies in Drug Discovery for Soluble Protein Targets

摘要

A vast number of technologies are currently available for the development of assays for soluble protein targets that are high throughput screening compatible. These assays are usually developed in microtitre plate format so that large numbers of compounds can be evaluated in a timely manner. In addition, for many assays, various components need to be labelled so as to allow target activity to be monitored. Upon completion of a screening campaign, the activity of a selection of hits are confirmed in a variety of secondary assays, some of which may be label-free and thus potentially of more physiological relevance. In this context, the successful application of label-free assays for the kinase, protease and histone deacetylase class of soluble enzyme targets will be discussed. Notable applications of these label-free assays include HPLC, isothermal titration calorimetry, surface plasmon resonance and NMR. In addition, the application of pseudo-label-free assays, in which the key biological event occurs in a label-free environment but the detection of target activity requires a label will also be discussed.