Graduate Program
Chemistry
Degree Name
Master of Science (MS)
Semester of Degree Completion
Spring 2025
Thesis Director
Michael W. Beck
Thesis Committee Member
Gopal R. Periyannan
Thesis Committee Member
Cesar A. Ortiz-Ledon
Abstract
This thesis focuses on the significance of subcellular location-specific activity of hydrolases, exploring their implications for drug-drug interactions (DDIs) and sequence polymorphisms in drug metabolism. Hydrolases exhibit distinct distribution patterns across various tissues and organs, playing pivotal roles in local metabolic processes. These enzymes possess a wide substrate scope, efficiently breaking down various functional groups found in biological molecules through the mechanism of hydrolysis.
Here, I explore the development and characterization of fluorogenic chemical tools tailored for investigating human carboxylesterase 1 (CES1) activity in live cells. CES1 plays an essential role in the hydrolysis of many pharmaceuticals, impacting drug metabolism and therapeutic efficacy. Despite the significance of CESs, limited techniques are used for studying their activity in live cells. My initial studies focused on the development of two fluorogenic compounds based on 3-O-methylfluorescein. My efforts determined that one of these compounds, MCP-Et, is non-toxic and specific for CES1 over CES2 in live cells. Harnessing this specificity I utilized MCP-Et to study CES1-mediated DDIs.
I next studied a library of fluorogenic acylmethoxy ether (AM)-esters. Upon in vitro screening of the library, multiple AM-esters showed specificity towards CES1. Compounds that showed strong fluorescence with CES1, but minimal activity with CES2 were prioritized for further analysis as selective chemical tools for CES1. The fluorescein-based fluorogenic chemical tools developed in this thesis will provide researchers with valuable tools to study CES1 activity in live cells, enhancing our understanding of its role in drug metabolism, resulting in better outcomes for patients treated with CES1-metabolized drugs.
Recommended Citation
Adusah, Emmanuel, "Identification of New Fluorescein-Based Chemical Tools for Studying Human Carboxylesterase 1 (CES1)" (2025). Masters Theses. 5088.
https://thekeep.eiu.edu/theses/5088
