Implementation of a Weak-Affinity Chromatography coupled to Mass Spectrometer (WAC-MS) fragment screening platform for academia and industry

Weak-Affinity Chromatography coupled to mass spectrometry (WAC-MS) is a technique of rising applications in drug discovery, where proteins of interest are bound to a support to form an affinity column, and small molecules are eluted in the mobile phase where they can be separated based on their different retention times.1,2,3,4. The method is already being offered as a service by companies specialized in fragment screening abroad5,6. In this work, we demonstrate the development of WAC-MS using previously defined ligands of the quinase protein MRCK-γ. We advanced this screening platform by implementing fragment screening with library composed of >1500 fragments, using two test proteins: BICC1 and ASCC3. Orthogonal assays are being developed and optimized to follow up on fragment growth. We expect that our Center for Medicinal Chemistry (CQMED) can act as a national reference lab for WAC-MS fragment screening and accelerate drug discovery, together with academia and industry.