Project Description
Objectives: The objective of this project is to design and synthesize hydrogen peroxide (H₂O₂)–responsive small-molecule DNA-damaging agents that are selectively activated in the oxidative environment of cancer cells. Elevated levels of reactive oxygen species (ROS), including H₂O₂, are a hallmark of many tumors and provide an opportunity for site-specific drug activation. By masking potent DNA-damaging warheads with ROS-cleavable protecting groups, this project aims to enhance cancer selectivity while minimizing systemic toxicity.
Methodology: The undergraduate researcher will synthesize a small library of H₂O₂-activated prodrugs incorporating boronate-based triggers that undergo oxidative cleavage in the presence of H₂O₂. The project will proceed through the following stages:
-Chemical synthesis: Multi-step organic synthesis of prodrug candidates using standard laboratory techniques, including reaction setup, purification by column chromatography, and yield optimization.
-Structural characterization: Product verification using NMR spectroscopy, mass spectrometry, and TLC analysis.
-Chemical activation studies: In vitro assays to confirm H₂O₂-triggered conversion of the prodrug into the active DNA-damaging species.
-Preliminary biological relevance: Evaluation of stability under non-oxidative conditions to assess selectivity for ROS-rich environments. Throughout the project, the student will be trained to understand the broader scientific rationale behind prodrug design, not just the individual reactions.
Tasks and Responsibilites
The undergraduate student will be responsible for carrying out the synthesis and characterization of H₂O₂-activated prodrug candidates under the supervision of the faculty mentor and graduate researchers. Specific responsibilities include preparing reaction mixtures, conducting multi-step organic syntheses, and purifying products using standard laboratory techniques such as column chromatography and thin-layer chromatography (TLC). The student will characterize synthesized compounds using NMR spectroscopy and mass spectrometry, analyze experimental data, and maintain accurate laboratory records in an electronic or written lab notebook. The student will also participate in regular lab meetings, discuss experimental progress, troubleshoot challenges, and revise experimental plans as needed. In addition, the student will be expected to follow all laboratory safety protocols, complete required safety training, and present a summary of their research findings at the conclusion of the SURF program.
Desired Qualifications
None listed.