Scott Rychnovsky

Scott Rychnovsky is a Distinguished Professor in the Department of Chemistry at the University of California, Irvine (UCI). His research focuses on chemical biology, synthetic organic chemistry, and the development of advanced mass spectrometry techniques for studying protein interactions and structural biology. He leads a research group pioneering cross-linking mass spectrometry (XL-MS) methodologies, including the design of MS-cleavable cross-linkers to map protein-protein interactions in living cells. His work integrates synthetic chemistry with proteomics, enabling large-scale analysis of cellular networks and dynamic protein complexes.

Rychnovsky’s group has contributed innovative tools such as sulfoxide-containing cross-linkers and trioxane-based reagents for high-resolution structural analysis. His research also spans total synthesis of complex natural products (e.g., strasseriolides, illisimonin A) and mechanistic studies of organic reactions, including gold-catalyzed spirocyclizations and Diels-Alder cyclizations. His lab has explored applications in drug discovery, such as reactivating p53 tumor suppressor mutants and developing antimalarial agents.

Key achievements include defining the structural dynamics of the human COP9 signalosome and 26S proteasome under oxidative stress using quantitative XL-MS. He has developed methodologies for absolute configuration determination of chiral molecules using competing enantioselective conversion (CEC) methods, advancing structural elucidation in organic chemistry. Rychnovsky has secured NSF funding and contributed to undergraduate education through innovative lab experiments for stereochemical analysis.

His research bridges synthetic chemistry innovation with cutting-edge proteomic tools, addressing fundamental questions in cell biology, enzymology, and drug design. Ongoing projects focus on expanding XL-MS applications for systems biology and creating next-generation cross-linking agents for in vivo studies.