Combinatorial library methods not only offer great potential for facilitating the drug discovery process but also provide powerful tools for basic research in various disciplines. These methods enable investigators to generate large number of chemical compounds that can be used as valuable source for the discovery of drug leads, molecular imaging agents, and capturing agents for molecular markers. In the area of basic research, large collections of chemical compounds can be used to probe their effects on specific cellular function. In the past 4 years, the combinatorial chemistry developing core has been assisting several Cancer Center investigators in the application of combinatorial chemistry to their research. These efforts have resulted in the submission and funding of several extramural grants. Based on the encouraging outcome and suggestion by our external advisory board, we plan to advance the combinatorial developing core to a full shared resource. The proposed combinatorial chemistry shared resource (CCSR7) will provide training and support for cancer center members to apply the ultra-high throughput one-bead-one-compound (OBOC) technologies for their research. Many OBOC combinatorial libraries (peptides, peptidomimetic, glycopeptides, small molecules, macrocyclic and glyco-organic libraries) will be designed and synthesized by the CCSR7 scientists. We have proposed to develop twenty-seven OBOC chemical libraries over the five year period. CCSR7 will also provide synthetic organic and medicinal chemistry expertise on working with the resource users for optimization of the lead compounds. CCSR7 will also provide synthetic organic and medicinal chemistry expertise on working with the resource users for optimization ofthe lead compounds.

Through training and support by CCSR7, cancer center investigators will have the opportunity to apply the enabling OBOC combinatorial technology for their research. It is expected that chemical molecules useful for cancer research and lead compounds for the development of cancer therapeutic and imaging agents will be discovered through such efforts.