The field of chemical genetics uses small molecules to perturb and study biological systems. In order to obtain a diverse and complex selection of compounds appropriate for chemical genetic analyses, innovative synthetic approaches must be developed. This proposal describes a conceptually novel method for the rapid synthesis of skeletally and stereo chemically diverse small molecule probes, drawing its inspiration from the structural diversity seen in biological macromolecules. To this end, reactive monomers will be assembled into oligomers and subjected to chemical transformations that cause them to """"""""fold"""""""" into covalently bonded, rigid structures. Depending upon the identity of the monomers employed and their position within the oligomeric chain, chemical transformation can give rise to skeletally and stereo chemically distinct molecular entities. Proposed small molecule skeletons have been engineered to resemble known natural products with the hope of maximizing compatibility with biological targets. These compounds can be screened against a number of disease states; initial screening efforts will focus on processes relevant to cancer.
