Organic / medicinal chemistry and chemical biology
The research group led by Prof. Blake R. Peterson at Ohio State creates chemical tools for the study of cancer biology and other biological systems. Our research is supported by association with the OSU Comprehensive Cancer Center, the OSU Pelotonia Institute of Immuno-Oncology (PIIO) (https://cancer.osu.edu/for-cancer-researchers/research/research-institutes-and-centers/pelotonia-institute-for-immuno-oncology), and the OSU Center for Cancer Engineering (CCE-CURES) (https://cancer.osu.edu/for-cancer-researchers/research/research-institutes-and-centers/center-for-cancer-engineering).
We conduct interdisciplinary research in the fields of bioorganic / medicinal chemistry and chemical biology to investigate anticancer agents, molecular probes, methods for therapeutic targeting, and tools for target identification. Our expertise includes the synthesis of steroids, lipids, nucleosides, peptides, heterocycles, fluorophores, and protein conjugates, and the evaluation of these compounds in biochemical assays, whole cell assays, and model organisms. We are increasingly using high throughput and high content screening available through the OSU Medicinal Chemistry Shared Resource (https://cancer.osu.edu/for-cancer-researchers/resources-for-cancer-researchers/shared-resources/medicinal-chemistry) High Throughput Screening Core (https://u.osu.edu/highthroughputscreeningcore/) to identify starting points for the development of drugs and probes. Our goal is to identify new therapeutic approaches and mechanisms. Two of our current research interests are described below.
Subcellular targeting for anticancer and phenotypic drug discovery
Modern research in the pharmaceutical industry emphasizes cellular targeting as a strategy to improve the therapeutic index of anticancer agents. However, drug targets reside in specific subcellular locations, and the design of agents that might gain additional potency and selectivity by accumulating in specific subcellular compartments is relatively unexplored. We investigate small molecules that accumulate in specific organelles such as the endoplasmic reticulum to target receptors sequestered in these specific cellular compartments (Angew. Chem. Int. Ed. 2015, 54, 9696-9699) and develop sensitive sensors of biological processes such as activation of macrophages (ACS Chem. Biol. 2018, 13, 2595-2602). We are additionally investigating the combination of traditional cellular targeting agents with novel compounds that disrupt membranes of endosomes to create new types of synergistic anticancer agents (ACS Omega 2019, 7, 12955-12968). We are currently using subcellular-localized fluorescent probes in phenotypic high throughput and high content screening campaigns to identify small molecules with anticancer activity. Hits identified through this approach can be used to identify new protein targets for cancer drug discovery.