Using Catalyst-Substrate Coimmobilization for the Discovery of Catalysts for Asymmetric Aldol Reactions in Split-and-Mix Libraries

“Catalyst–substrate coimmobilization” has been used for the discovery of highly active and selective peptidic catalysts for asymmetric aldol reactions within split-and-mix libraries. This screening method is based on the coimmobilization of one reaction partner along with each library member via a bifunctional linker on the library beads followed by mixing of this library with a labeled second reaction partner. Here we discuss the details of the combinatorial screening and demonstrate that the exchange of the bead-bound and the labeled reaction components leads to the same hits within the library.