A core facility for the synthesis of combinatorial peptide libraries will be established. The core facility will be equipped with an Advanced ChemTech model 357 Biomolecular Synthesizer. This instrument has the capability to synthesize sets of peptides in parallel and also in the spit-and-pool mode to afford combinatorial peptide libraries. The instrument will be operated and maintained by a dedicated research scientist who will implement the combinatorial peptide synthesis methodology. The core facility will be used by students and post-doctoral investigators from the component projects as a resource to prepare peptide libraries directed toward their respective targets. The research scientist in the core will serve as the focus of the combinatorial methodology and provide advice on the library synthesis, screening, and analysis to the individual project. The goal of the core facility is to facilitate the generation of chemical diversity using the will established chemistry of peptide bond formation. Natural and non-natural residues will readily be incorporated during combinatorial ligand synthesis. The sequencing of peptides beads after screening will be facilitated by using a partial termination strategy that will allow peptide sequence to be determined from a single mass spectrum. This approach allows the rapid identification of new ligands for their respective targets for each component. In addition, the combinatorial approach will allow the generation of rapid feedback to test the theoretical design criteria developed using computational methods.
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