Chemical Biology Core Facility

Parallel pipetting of samples in 384 well format

Small molecules play essential roles in many areas of basic research and are often used to address important biological questions. The aim of our Chemical Biology Core Facility is to enable research groups to address biological questions by identifying and developing 'biotool' compounds against novel targets. We can assist groups in the development of primary and secondary assays for screening against our in-house compound library and guide them through the process of developing tool compounds for their specific target. Chemical optimisation projects can be done in collaboration with our chemistry partners.

The facility is a collaboration between EMBL and the DKFZ (German Cancer Research Center, Heidelberg) to provide the infrastructure and expertise to open up small molecule development to research groups at both institutions.

Major projects and accomplishments

The facility was established at the beginning of 2004. Through a large team effort, it was fully functional in August 2004. We have a very strong pipeline of projects from EMBL and DKFZ, several of which have completed screening and are now in the lead optimisation phase.

Services provided

The new Chemical Biology Core Facility screening library is composed of 79,000 compounds. The selection focused on compound catalogues from three leading vendors in the field. Each vendor offers access to significantly larger collections with low redundancy and highly competitive prices coupled with attractive options for resupply and follow-up synthesis services. The selected compounds were checked for drug-likeness, structural and shape diversity, novelty and compliance with medicinal chemistry requirements. Individual compound selection was done by picking representative compounds around selected scaffolds. A scaffold-based selection offers the advantage of high information screening: since the structural space around each scaffold is covered appropriately, any hit compounds from a high-throughput screen can be rapidly followed up by selecting similar compounds to enable initial structure-activity relationships to be discerned. This will help in the prioritization of the hit compounds for further medicinal chemistry optimisation.

Further services include:

• Selection of appropriate assay technology platforms.
• Developing assays for medium-throughput screening.
• Assisting in the design of secondary specificity assays.
• Compound characterisation.
• Managing compound acquisition through our chemistry partners.

Partners

• Technology partners: Perkin Elmer, IDBS.
• Chemistry partners: Tripos Inc. and Tripos Discovery Research Ltd.