In this project in the Organic Dynamics Program of the Chemistry Division, Dr. Donald Hilvert of the Scripps Clinic Research Foundation will continue to investigate the rational design of catalysts. Reengineering existing macromolecules using chemical or genetic techniques represents a powerful strategy for constructing new active enzyme sites. This research project will focus on the synthesis and study of semisynthetic selenoenzymes. This research project is focussing on the continuation of Dr. Hilvert's successful program to synthesize and study semisynthetic selenoenzymes. The molecular properties of selenium makes it an excellent probe of steric and electronic factors that influence the reactivity of oxygen and sulfur nucleophiles in proteins. Artificial selenocysteine-containing enzymes are also useful models for mimicking and understanding the redox chemistry of the naturally occurring selenoenzyme glutathione peroxidase, which protects mammalian cells from oxidative damage. The value of organoselenium compounds in organic synthesis is also being studied and a detailed investigation of the physicochemical and structural properties of the first artificial selenoenzyme (selenosubtilisin) is in process.
