The use of chemical tools has become an increasingly important strategy to probe and manipulate biological systems.  One class of chemical tools relies on self-immolative linkers to achieve their function.  Self-immolative linkers are chemical moieties that connect a masking group to a chemical cargo.  Upon a reaction with a biomolecule that cleaves the masking group, self-immolative linkers release their chemical cargo.  Such self-immolative linkers have found use in prodrugs and in chemical sensors, but are often limited by slow kinetics of release.  Our lab has investigated the use of phthalate esters as a new class of self-immolative linkers with very fast release kinetics in water.  The use of chemical masks sensitive to fluoride, light, and non-covalent stimuli have been used to test the utility of these phthalate esters as self-immolative linkers.  We have also synthesized extended domino self-immolative linkers based on these structures that may allow these molecules to find use as chemical amplifiers, wherein a single mask-cleaving reaction leads to the release of multiple cargo molecules.   Additionally, our work on the synthesis of molecules with switchable paramagnetism will be discussed.   Such molecules with switchable paramagnetism may find applications as EPR sensors for diamagnetic biomolecules.

Chemical tools for biological applications: A physical organic chemistry approach

248th National Meeting (2014)

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