Mentor: Dr. William Malachowski
Indoleamine-2,3-dioxygenase (IDO) is an enzyme that degrades tryptophan, an amino acid found in the body that is essential to T cell function and the body’s immune system. It was recently discovered that IDO is expressed to protect a fetus from attack by the mother’s immune system, and in the same way is expressed by tumor cells to suppress immune response. Therefore, if an effective inhibitor of IDO could be applied, the cancerous cells would no longer be protected from the body’s local immune system functions.
Design and synthesis of possible inhibitors of IDO is the focus of this project, and a variety of indole (1) derivatives and tryptophan (2) analogs have been synthesized and tested. Thus far, the biological analysis performed at the Lankenau Institute has shown that compounds with a molecular structure similar to brassinin (3) have shown the most effectiveness in inhibition testing. Synthesis of more compounds using tryptamine (4) while varying the size and composition of substituent groups will allow further evaluation of which types of compounds are the most effective inhibitors.
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