New bioorthogonal self-immolative linker based on the Grob fragmentation reaction

We have designed and synthesized a new self-immolative bioorthogonal cleavable linkerbased on the Grob fragmentation reaction that allows the controlled release of sulfonate-containing compounds such as a dansyl group under physiological conditions. We have alsotuned conveniently the pKa of the pushing group (amino group) using different substituents,leading to more efficient conversions at physiological pH and in some cases even at acidicpH, which is normally found in tumour environments. In addition, the Grob fragmentationtakes place under physiological conditions in living cells, demonstrating the potentialbioorthogonal applicability of the reaction. Based on these promising results, research iscurrently underway to incorporate this type of linker into antibodydrug conjugates for thetargeted delivery of cytotoxic drugs and fluorophore