DEVELOPMENT OF SEQUENTIAL CLICK REACTIONS: NEW PERSPECTIVES IN TARGET-GUIDED-SYNTHESIS? – Click_and_Fish

The bioorthogonal and click chemistry toolbox provides a set of reliable chemical reactions enabling the chemoselective covalent bond formation between two chemical entities without interfering with other existing (bio)functionalities. In the space of a decade, these transformations have dramatically gained importance from Life Sciences to Environmental or Material Sciences. Due to an increasing demand for effective and modular accesses to complex (bio)molecular architectures, the development of a “second generation” of click reactions is envisioned, based on innovative successive bioorthogonal reactions. The usefulness of this strategy will be demonstrated in kinetic target-guided synthesis (KTGS), a promising alternative to high throughput screening, which still suffers from severe limitations (i.e. self-poisoning of the biocatalyst) that dramatically hampers its routine use in both academic and R&D environment.