Mentor: Rock Mancini, Ph.D.

Chemotherapy is regarded as one of the most common cancer treatments, but fails in almost 90% of cases due to acquired resistance against anti-cancer drugs (1). The development of Multi-Drug Resistance (MDR) is a common limitation in all cancer treatment modalities, however, (1). Immunotherapy is a promising pathway in MDR cancer treatment for its ability to boost the body’s own immune system to attack and destroy cancer cells. Proximity-accelerated chemistry is a strategy used to speed up chemical reactions when the reactants are held in close proximity. This technique has been modified to produce the Ligand-Directed Nitrophenol Carbonate (LDNPC) chemistry seen in Figure 1 (2). In this method, a chosen ligand is conjugated to a nitrophenol carbonate and a self-immolative linker, which is attached to the drug payload (2). As the ligand binds to the target, nucleophilic residues peripheral to the binding site attack the molecule (affinity labelling). The linker is subsequently hydrolyzed, releasing the drug payload.

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