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Show 82 Levon Katsakhyan college of science Wnt signaling pathway has a fundamental role in cell differentiation, proliferation and cell-cell communi-cation. It drives the activation of specific target genes and is generally considered to be more relevant to the differentiation and self-renewal of cancer stem cells. β-catenin is a central component of the signal-ing cascade where it forms a complex with T-cell factors. The prominent accumulation of the β-catenin/ Tcf complex is the uniform feature of tumorigenesis. The crystal structure of β-catenin bound to the Tcf-4 factor is analyzed with computer modeling software, identifying a basic scaffold and critical binding sites. The Ji research group has many ways of synthesizing the scaffold in the laboratory and manipulating many groups of the scaffold to search for potent and selective inhibitors. The goal is to synthesize an inhibitor that selectively binds to the β-catenin protein and inhibits the binding of Tcf-4 without interrupting other interactions with the protein such as Adenomatous polyposis coli or E-cadherin. To establish this specific binding, scaffolds are optimized according to the estimated binding affinity from computer modeling, utilizing more interactions than the native Tcf-4 factor, and thus successfully inhibiting it. Multiple scaffolds have been developed by the Ji research group that demonstrate biological activity. Cur-rently efforts are being made to increase the biological activity of these scaffolds and create new ones that target different binding pockets. STRUCTURE BASED DESIGN OF SMALL MOLECULES TO SELECTIVELY INHIBIT PROTEIN-PROTEIN INTERACTIONS OF β-CATENIN AND T-CELL CATOR IN THE WNT/ β-CATENIN CELL-SIGNALING PATHWAY Levon Katsakhyan (Zheng Huang, Haitao (Mark) Ji) Department of Chemistry University of Utah UNDERGRADUATE RESEARCH ABSTRACTS Zheng Huang Haitao Ji |