Chemical Biology : Chemical probes

Peptide Chemistry STP

Chemical probes

We work with our collaborators to give guidance of the tractability of a protein target and on the appropriate modality for perturbing its function. We have experience in small molecules, linear and cyclic peptides, degraders and antibody-drug conjugates.

The group has expertise in Synthetic and Medicinal Chemistry, which we apply to optimise hits from compound screens and early chemical starting points. We collaborate with other STPs, such as HTS and Structural Biology, to optimise the potency, selectivity and physicochemical properties of these modulators for precise application in cell-based systems and, if required, animal models. We also provide guidance on the design, selection and sourcing of small molecule screening libraries for biochemical and cell-based screens.

Where required, we develop these tools into probes with additional functionality, such as reactive warheads, fluorophores, affinity tags for enrichment or handles to enable click chemistry.

When there are existing tools available for a particular biomolecule, the group provides consultancy and training to Crick scientists on selection, evaluation and application of high-quality chemical probes. An overview of a selection of relevant publicly available resources is outlined below.

Chemical Probes Portal, an expert review-based public resource to empower chemical probe assessment, selection and use. The latest paper, published in Nucleic Acids Research, updates the scientific community on the development of an enhanced version of the portal.

Structural Genomics Consortium unique open science project discussed in 2018 eLife 7:e34311, originally initiated by several pharmaceutical companies (AbbVie, Bayer, Boehringer Ingelheim, Janssen, MSD, Pfizer, and Takeda) makes innovative high-quality probes openly available to the research community.

A word graphic showing target and compound related criteria applied by the Structural Genomics Consortium.

Chemical Probes Criteria from Science Forum: Donated chemical probes for open science, eLife 7:e34311

The Chemical Biology facility provides a training course to Crick scientists that covers this material in more detail and provides hands-on experience of identifying probes of interest in the public domain.