MS-based screening
Screening compound libraries by mass spectrometry is highly attractive due to its direct readout, high throughput and truly label-free nature. Our high-throughput capabilities with MALDI-MS enable efficient screening of large compound libraries (100k-1m), while LC–MS (RapidFire) is ideal for orthogonal screening or smaller, focused libraries. This flexibility allows us to optimise your screening process, helping ensure faster and more accurate results at any scale.
For new covalent inhibitors, we use intact mass measurement of the target protein after incubating covalent warhead library members at fixed times and protein-to-compound ratios. A robust electrospray time-of-flight instrument is employed for this purpose. We further validate hits over time, using the protein of interest with targeted amino acid mutations as negative controls when available. Alternatively, we perform peptide mapping to identify the modified amino acids on the target protein.
To prioritise your hits for lead optimisation, we determine the kinact/KI value, a critical parameter describing the efficiency of covalent bond formation. Additionally, we use MALDI-MS and short model peptides containing reactive amino acids (e.g., cysteine) to test the reactivity of new or unknown covalent warhead libraries. This comprehensive approach helps ensure that you receive reliable data to drive the development of your therapeutic candidates.
