Chemical probes for studying cyclooxygenase-2 and nitric oxide in living systems

Molecular imaging enables the direct detection of analytes and biomolecular species within their native biological environment. Although the field derives from diagnostic biomedical imaging, there has been a significant shift over the past couple decades towards using imaging to evaluate and discover biology. In general, molecular imaging relies on the development of chemical or biochemical tools that accumulate at the site of interest or under undergo a selective, observable change following target engagement. Activity-based sensing is a powerful expansion of molecular imaging because it measures chemical reactivity rather than concentration. Chapter 1 serves as an introduction to molecular imaging with a historical tone. It also defines and highlights key examples of binding-based and activity-based sensing probes to contextualize the following chapters. Chapter 2 discusses the design and validation of a fluorescent probe for detecting cyclooxygenase-2 activity with live cells, as well as the discovery of oxygen-dependent regulation that is not observed on the protein expression level. Chapter 3 summarizes our progress towards the development of photoacoustic probes for imaging nitric oxide within live animals. Topics include the preparation of a photoacoustic probe for imaging nitric oxide in a small animal model of inflammation, the optimization of the aza-BODIPY dye platform to detect cancer-derived nitric oxide, and progress towards a multimodal dye platform for photoacoustic and fluorescence imaging.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2020

Author dc:creator

• Reinhardt, Christopher J.

Contributors dc:contributor

• Chan, Jefferson
• Gerlt, John A.
• Hergenrother, Paul J.
• van der Donk, Wilfred A.

• molecular imaging, reaction-based chemical probes, activity-based sensing, cyclooxygenase, nitric oxide, fluorescence imaging, photoacoustic imaging

Statement dc:rights

• Copyright 2020 Christopher J. Reinhardt

Language dc:language

en

Handle dc:identifier

http://hdl.handle.net/2142/108487

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/108487