Summer Science Research 2013
Bryn Mawr College
Abstract: Eun-young Park
Mentor: William Malachowski
Indoleamine-2, 3-dioxygenase (IDO) is an immunosuppressive enzyme present in high levels in cancer patients, linked to a decrease in T cells due to apoptosis. Research suggests that the inhibition of IDO can improve the effective of cancer treatment such as chemotherapy or radiotherapy.
Previous work has been done in synthesizing and evaluating small molecule inhibitors of IDO. Biaryl hydroxylamine has found to be the most potent IDO inhibitor with an IC50 value of 186 nM. However, this IC50 value is based off a racemic mixture of both the R- and S- enantiomers of biaryl hydroxylamine, which is a chiral compound. This can dramatically affect a patient based on the dosage amount of this potential IDO inhibitor compared to a potentially lesser dosage necessary based on the more effective enantiomer of biaryl hydroxylamine. Therefore, research will be conducted this summer in synthesizing asymmetric biaryl alcohols by developing and utilizing chiral catalysts. Then, IC50 values of R- and S-biaryl hydroxylamine can then be evaluated in future tests by our biological collaborators in order to determine the most potent small molecule IDO inhibitor.
Also known in literature is the natural IDO substrate, 1-methyl-tryptophan. My summer research will also involve the synthesis of a compound that mimics 1-methyl-tryptophan. This synthesis will be carried out through tests and evaluations of different coupling reactions. I hope to also add an epoxide group to this synthesized compound, which will be evaluated for further research by a biochemist at the Albert Einstein College of Medicine of Yeshiva University in Bronx, New York.