Author ORCID Identifier
Year of Publication
Master of Science (MS)
Arts and Sciences
Dr. Samuel G. Awuah
Indoleamine 2 3-dioxygenase (IDO) has recently been highlighted as a promising target for small molecule based immunotherapy. IDO is often coopted by various cancer cells to promote an immune-suppressive environment around tumors. DNA damage repair (DDR) enzymes have recently been targeted for inhibition to promote genetic instability and bolster immune recognition. DDR enzymes such as PARP and POLγ are common inhibition targets due to their direct effects on cellular function. In the process of designing conjugate inhibitors of IDO and DDR enzymes, novel synthetic methodology was developed for the mild deprotection of N-Tert-butyloxycarbonyl (N-BOC) group from various amines. Conjugate inhibitors of IDO and PARP were synthesized using the parent molecules 1-MLT and Olaparib. The conjugate molecules showed more potent cytotoxicity in various cancer cell lines than their precursor molecules. The novel conjugate inhibitors could be used as probes to explore interplay between the PARP and IDO signaling pathways and elucidate any synergy or dependency between the two enzymes.
Digital Object Identifier (DOI)
University of Kentucky, Start up funding. 2016
George, Nathaniel, "Synthesis of Dual Small Molecule Hybrids to Probe the Synergy between DNA Repair Enzymes and IDO1" (2021). Theses and Dissertations--Chemistry. 140.