Oral Presentation HUPO 2019 - 18th Human Proteome Organization World Congress

Unraveling protein targets of bioactive small molecules using label-free chemical proteomics (#225)

HoJeong Kwon 1
  1. Yonsei University, Seoul, South Korea

Identifying protein targets of bioactive small molecules and deciphering the specific mechanisms-of-action at the molecular level are crucial steps in the development of drugs to treat human diseases. We have developed target protein identification methods including conventional affinity chromatography using labeled small molecules as well as recent target identification method with label-free small molecules such as Drug Affinity Responsive Target Stability (DARTS) in combination with LC-MS/MS analysis to identify the direct binding proteins of small molecules. The direct interaction between small molecule and the target protein is validated via bio-physical, and bio-informatics methods. Moreover, biological relevancy of this “small molecule-target” interaction is validated through genetic modulation study and facilitates structure based better drug development. In this presentation, our recent studies on target identification of bioactive small molecules for exploring new mechanism studies and translational applications will be presented by introducing our case studies of protein target identification and validation of bioactive small molecules from natural products and clinical drugs.