Leveraging Small Molecules for Biology and Therapy - discovery of novel tetracycline antibiotics and inhibitors of histone lysine methyltransferases

Small-molecule probes serve as unique tools to study biological questions and offer great promise toward therapeutic applications. This talk will present two examples using complementary strategies to develop small-molecule probes, including: (1) the discovery of novel tetracycline antibiotics to overcome the drug resistance in a “top-down” approach; and (2) the identification of small-molecule inhibitors of histone lysine methyltransferases in a “bottom-up” fashion. The principles in synthetic chemistry, assay development, genetics and proteomics have been integrated to facilitate the discovery of such useful probes. Especially, synthetic efforts, such as the synthesis of complex molecules and the development of novel chemical transformations, have been playing an important role.