Chemical Biology : Target identification

Peptide Chemistry STP

Target identification

We collaborate with Crick research groups and other facilities, such as High Throughput Screening, to validate chemical hits from phenotypic, cell-based assays hits and contribute to building a body of evidence to identity the molecular mechanism of action by which the compound is exerting its biological effects.

This would typically involve an assessment of any PAINS (Pan-Assay INterference compounds) motifs, alongside exploring the structure-activity relationships associated with the chemical hit. If required, the group can also provide guidance on characterisation in additional orthogonal assays required to build confidence in the robustness and validity of a hit compound.

Targeted chemogenomic sets may be designed and applied to explore any putative biological targets thought to be responsible for driving the observed phenotypic effects of chemical hits. This involves the screening of different compound chemotypes acting on the same biological target, in addition to their corresponding negative controls, where available. This evaluation of the phenotypic data obtained should reveal any commonalities in response that suggest the compounds are mediating their effect via the same target.

Further functionalisation of compounds of interest can be designed and synthetically incorporated, to enable pull-down/enrichment in chemoproteomic workflows. This is carried out in collaboration with proteomics, with the purpose of enabling the identification of the protein targets that the compound is binding to in a cell-based environment.