Combination Of Mass Spectroscopy With Fragment Based Drug Discovery Emerges As A Powerful Tool For Discovering Drug Leads

The Griffith Institute for Drug Discovery (GRIDD), Griffith University, Brisbane, is an example of one laboratory using High Throughput Screening (HTS) robotics for automated screening, to increase the overall speed of drug discovery. Researchers use it for the rapid identification of large numbers of active compounds, which are then assessed by their ability to influence a particular biological pathway and to emerge as a new drug. Complementary to HTS is Fragment-Based Drug Discovery (FBDD) that has emerged as a powerful tool for discovering drug leads. This approach must first identify very small molecules (fragments) that bind to proteins. GRIDD focuses on combining mass spectrometry (MS) with FBDD, to observe fragment-protein interactions to identify these superior starting points for drug discovery.

As per reports in R&D, fragment screening capabilities are significantly improved through Magnetic Resonance Mass Spectrometry (MRMS), previously known as Fourier Transform Mass Spectrometry (FTMS). The extreme resolution afforded by MRMS provides an extra layer of confidence in fragment screening as protein-fragment interactions are very weak interactions.

Whereas other fragment screening techniques suffer from producing high false positives as they having to deal with the fragments at high concentrations, MRMS produces minimal false positives. When fragments are at higher concentrations, they can aggregate and behave irregularly. When using MRMS, the fragment is at a similar concentration as the protein, so false hits are less likely to occur, which is highly advantageous. The MRMS method can quickly rule out ineffective compounds to avoid wasting valuable time on compounds that will not advance along the discovery and development pipeline.