October 26, 2023 11:00 am
October 26, 2023 12:00 pm
At the Nexus of Stereocontrolled Synthesis, Enzymology & Chemical Biology
David Berkowitz
Willa Cather Professor of Chemistry
University of Nebraska
This seminar will highlight the interplay of synthetic organic chemistry and mechanistic enzymology in our laboratory. On the one hand, we seek to co-opt active site chemistry for stereocontrolled synthesis, directly in hybrid bio/chemocatalytic ventures and indirectly by using enzymes as catalytic reporters to facilitate the discovery of new organic/organometallic catalysts in an in situ enzymatic screening (ISES) approach to reaction development. Examples will be given in which sets of alcohol dehydrogenase enzymes are used to facilitate the catalyst/ligand screening process, and in which an alcohol oxidase/peroxidase reporting enzyme tandem has allowed us to uncover new reaction modalities, including novel bromorhodiation-carbocyclization & thiocyanopalladationcarbocyclization transformations. On the other hand, we are targeting active site chemistry in the design, synthesis and evaluation of new types of mechanism-based inhibitors (MBIs). We have developed chemistry that provides access to families of quaternary, a-(1’fluoro)vinyl- and a-(2’Z-fluoro)vinylamino acids, bearing the side chains of the cognate amino acids (AAs). As a result, the a-(1’fluoro)vinyl trigger originally proposed by Abeles and the a-(2’Zfluoro)vinyl trigger are now available in a quaternary AA context to be tested for their ability to inactivate selected vitamin B6-dependent enzymes. Recently, we have become particularly interested in PLP enzymes relevant to neuronal signaling, an area of great importance for chemical biology.