Abstract

High throughput capable MALDI-TOF MS has become an emerging analytical technology in drug discovery in recent years. Apart from being label-free, this technique is cost effective and represents a robust read-out for several biochemical assays in industrial settings. Cell-based MALDI MS assays are still underrepresented as they are more complex and difficult to automate and validate. However, they offer the rare possibility of analysing molecular reactions directly in the cellular context without the necessity of elaborate and time consuming separation methods for cellular components. In this talk, approaches and considerations for the development of MALDI MS cell assays in drug discovery are shown. Moreover, three example assays are presented to underline their strength: the profiling of epigenetic histone deacetylase inhibitors, a mechanistic cell-based assay that monitors inhibition of the fatty acid synthase directly in whole cells using the enzyme specific metabolite malonyl-CoA as FASN reaction readout and a compound screen for the identification of inhibitors of the uptake of estrone-3-sulfate through the transport protein OATP2B1.