Signal propagation from cell surface receptors is further amplified by diverse enzyme classes that create post translation modification on multiple target proteins e.g. phosphorylation, ubiquitination, methylation etc. These modifications are selectively recognized by distinct protein domains – mostly considered “un-druggable”. Selective modulation can be achieved downstream of an enzyme by inhibiting the recognition of site-specific post-translational modification via these distinct protein domains
o2h scientists have previously worked in identifying first-in-class inhibitors in the area of oncology with Prof. Ashok Venkitaraman at the University of Cambridge, UK and at the Center of Chemical Biology and Therapeutics, India.
Using state-of-the-art technology, we can assist in characterization of protein-protein interactions and functionally assess novel strategies of target modulation that are not amenable to classic modes of inhibition.
In the absence of chemical starting points, we could assist in developing inducible systems (e.g. Tetracycline (Tet) induced), expressing plasmids encoding fluorescent tags fused to either wild-type or mutant protein domains. Overexpression of these target domains, are predicted to mimic the action of chemical inhibitors by competitively suppressing the protein-protein interactions of endogenous full-length protein. This helps in addressing biological selectivity but also suggest the potential to modulate intracellular signalling with equivalent precision through the development of selective inhibitors.
Our portfolio of projects also include work in targeted degradation, covalent binders and nucleic acid-based approaches. Through our integrated drug discovery platform, we are able to develop new molecules from these classes in addition to characterising their functional impact on undruggable targets.
To know more about our biology services offering or to request our brochure, please reach out to us at discovery@o2h.com.
