We will establish a Synthetic Chemistry Core (SCC) facility that will synthesize small molecules and reagents essential for the work of Projects 1, 2, and 3. The SCC will synthesize reagents necessary for the creation of the small molecule libraries described in Project 1, including monomers, tags, and templates. Automated synthesizers will be introducer over time to increase monomer diversity and the speed with which new monomers can be generated. The SCC will also be responsible for resynthesizing libraries as they are consumed in the assays described in Projects 2 and 3. The SCC will organize the monomers that are synthesized for Project 1, and maintain a chemical stock facility for use by the entire Institute of Chemistry and Cell Biology. Analytical instrumentation used for the structural analysis of small molecules will be located predominantly within the SCC, and will be managed and maintained by members of the SCC. The SCC will be responsible for decoding the tags that are used to encode the synthesis strategies employed a library construction. The SCC will receive synthesis beads that have been assayed by Projects 2 and 3 and found to have biological activity. Once the tag is decoded, the SCC will resynthesize the appropriate small molecule, and return it to investigators in Projects 2 and 3. Once the activity of the small molecule is reconfirmed, the SCC will design a series of structural derivatives of the small molecule to enable structure-activity studies to be performed. The most active small molecule will then be synthesized in larger quantity by the SCC, for testing in additional biological assays and to send the compound to our collaborators for analysis. The Administrator Core A will coordinate compound shipments and communications will collaborators, and will provide administrative support and financial oversight to the SCC. The efforts of the SCC will be overseen by Prof. Matthew Shair, also a co- investigator of Project 1. The SCC will be managed by a chemist with experience in the are of split-pool synthesis, monomer synthesis, and encoding strategies. This individual will be responsible for managing the daily activities of the SCC, and will be a member of the ICCB steering committee.
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