Shinya Oishi (Kyoto Pharmaceutical University) Synthesis and Applications of Mirror-image Proteins to Drug Discovery

Natural products and their derivatives have been valuable resources for drug discovery. The desirable biological activities are attributed to the unique, complex, and sp3-carbon-rich scaffolds, which were originally produced by bacteria, fungi, plants, or others as secondary metabolites. These natural products bearing a chiral structure(s) are normally produced as a single enantiomer. We established a novel screening approach for a virtual “mirror-image library” of chiral natural products and their derivatives. In this process, the bioactivity of natural products was evaluated by chemical microarray technology using a synthetic mirror-image protein (D-protein). This examination corresponds to the screening of mirror-image natural products for a native protein (L-protein) in a mirror. This chemistry-driven approach facilitated the identification of unprecedented lead compound(s) from an unexplored mirror-image library of chiral natural products. In the seminar, our recent applications of this approach to mirror-image antibody-like proteins will also be presented.