Date of Award
5-11-2026
Document Type
Thesis
First Advisor
Adebowale Ogunjrin
Second Advisor
Paul Sabila
Abstract
Cancer is a significant problem and requires continued research, as it remains one of the leading causes of death worldwide (Ramos, 2021). This capstone explores the synthesis and preliminary evaluation of a nicotine-type compound as a potential cancer-curing agent targeting the PLK-1 PBD protein using fluorescence polarization. The hypothesis is that a specific ligand may contribute to cancer research. This project also reviews cancer management methods while illustrating the discovery of chemical drugs used in chemotherapy. The project involves synthesizing and testing 3-((1-methylpyrrolidin-2-yl)methoxy)-1-alkylpyridin-1-ium, known as Compound C, to determine whether it can function as a potential cancer management agent. The synthesis process includes designing, synthesizing, purifying, and confirming the compound's identity. Methods used include organic synthesis, nuclear magnetic resonance (NMR) spectroscopy to confirm structure, purifying products to ensure compound purity, and separating mixtures using column chromatography, a technique that uses layers of sand and silica gel. These steps produce a synthesized ligand that can be evaluated for its ability to bind to the PLK-1 PBD protein. Binding interactions are assessed using fluorescence polarization, which measures molecular rotation to detect binding. This technique was selected due to better safety, low environmental toxicity of equipment and materials, compared to radiation-based methods, which are not feasible because of safety and cost concerns. Fluorescence polarization, therefore, provides a quicker approach for evaluating ligand interactions in early-stage drug discovery. Results from the accelerated fluorescence polarization assay showed that at 1mM, Compound C produced 10% inhibition of the FITC poloboxtide ligand, indicating weak binding to the PLK-1 PBD domain. Although the compound did not exhibit strong inhibitory activity, the synthesis and testing process contributed to understanding ligand-protein interactions and provides insight for future ligand development.
Recommended Citation
Johnson, Carter, "Synthesis of a Nicotine-like Backbone Ligand for Binding Evaluation at PLK-1 PBD" (2026). Undergraduate University Honors Capstones. 143.
https://ida.gallaudet.edu/honors_capstones/143
