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We are developing novel medicines using our suite of proprietary technologies based on high-resolution mass spectrometry (MS) of intact protein assemblies. The technology enables detection of drug leads that not only bind to the target complex, but also exert a functional effect through modulation of complex formation – both of these effects (binding and function) are measured by a change in mass. These methods are being applied to drug discovery for membrane targets, including GPCRs.

The Company is a world-leader in native mass spectrometry that allows protein targets to be studied in a folded native-like state thereby preserving any associated non-covalent interactions. This allows drug interactions to be captured as well as the influence of those drugs on down-stream interaction networks that are necessary for dictating function. In this way, the technology enables direct observation of pharmacology (binding and function) at the un-precedented resolution provided by a biophysical method such as mass spectrometry.

Orthogonal MS approaches provide complementary insights to the drug discovery process. Hydrogen-deuterium exchange is capable to monitoring structural changes in response to binding – thereby revealing changes in conformational dynamics and mapping binding sites. A central focus of OMass is to also automate the native platforms for hit-finding activities, using both currently available technologies as well as new in-house approaches.

Native Mass Spectrometry

Protein assemblies are introduced to the mass spectrometer, using nano-electrospray ionization. The technique allows very accurate mass measurement whilst maintaining their native conformations and interactions with drugs.

Preserving Structure

Non-covalent interactions are preserved and detected.

Structural Mass Spectrometer Analysis

The resulting spectra allows the equilibrium between each component and complex formation to be captured, directly reporting on stoichiometry and ligand binding.

Labelling

A protein complex is introduced to a labelling solution, which labels solvent accessible areas of the assembly. Labelled areas of the complex can be identified due to the increase in mass induced by the label.

HDX

Regions involved in protein-protein interactions can be identified since they have a lower propensity to be labelled. This also enables identification of drug binding sites.

Screening with Native Mass Spectrometry

In a multi-well plate, the protein is incubated with a compound library. Using automated injection, each mixture is analysed by native mass spectrometry to check for binding.

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