Topic: Don’t ignore the linker: Self-immolative linkers in bioorthogonal chemistry and on-demand heterocycle synthesis

Abstract: 

Self-immolative linkers enable chemists and biologists to mask a chemical group required for function, with the added benefit of being able to control the removal of the group when required. However, there are still some issues with these types of linkers including: (1) non-optimal release kinetics and (2) generation of reactive by-products.

Our investigations into new and improved self-immolative linkers, which aim to address the shortcomings of current linkers will be presented. For example, we have developed a method for bioorthogonal activation of prodrugs, whereby the structure of the linker dictates the release rate of the drug. Also discussed will be our work investigating the potential to generate heterocycles in situ from the reactive linker by-products following activation and self-immolation of the prodrug.