Tagging molecules with linear polymers: Biocatalytic transformation of substrates anchored on soluble macromolecules

With the increasingly available technology in automated synthesis and screening protocols, the combination of polymer-supported chemistry and biocatalysis, with their respective advantages over classical organic synthesis, has become more scientifically attractive, yet remains challenging. Since the development of solid-phase synthesis and its rapid expansion in combination with the advent of combinatorial techniques, a variety of alternative methodologies have been proposed and demonstrated to be viable for applications in high-throughput and multistep syntheses of the desired products. These alternative methodologies overcome the disadvantages of crosslinked polymer beads, which, as a consequence of their insolubility and their being necessarily heterogeneous in the reaction mixture, do have operational drawbacks. They often rely on a common strategy: tagging the target substrate of interest with other fragments (fluorous synthons, macromolecules, "precipitons") in such a way that the tag-substrate covalent ensemble is then easily separated from the reaction mixture by physical methods (liquid-liquid extraction, precipitation, etc.). The efficiency of enzymes in transforming substrates is often enhanced when the stability limitations of the biocatalyst in unnatural conditions (i.e. organic solvents, high temperatures) are avoided by the use of immobilization-stabilization techniques. We comment here, with recent examples, on the use of linear macromolecules as recyclable tags capable of acting as covalent supports in combination with a biocatalyzed reaction.