Activity-based sensors for reactive aldehydes and their corresponding enzymatic machinery
type: CreativeWork
description: Molecular imaging agents are chemical tools that have become essential to the study of life. The field of molecular imaging encompasses a wide range of modalities and mechanism, but an exciting and growing subfield is that of activity-based sensing. Activity-based sensors provides new insights into biological processes since they report on the activity of biological species rather than just the presence. Naturally these are ideal probes for enzymes, affording multiple turnovers and higher signal from a single active enzyme. Activity-based sensors are also excellent sensors for reactive small molecules with unique chemical reactivity. Here, we report the development and/or progress on activity-based sensors for reactive biological aldehydes and the enzymatic machinery tasked with aldehyde metabolism. We first developed AlDeSense, the first turn on fluorescent probe selective for aldehyde dehydrogenase (ALDH) 1A1. We pursued a probe for this enzyme since it’s frequently cited as a cancer stem cell marker. AlDeSense had remarkable selectivity for ALDH1A1, producing a 20-fold increase in fluorescence signal upon oxidation by the enzyme. We confirmed ALDH1A1 activity, as measured by AlDeSense, was a reliable cancer stem cell marker in leukemia, melanoma, and breast cancer models. AlDeSense was then applied to image ALDH1A1 activity in aggressive and non-aggressive melanoma ex vivo and in vivo. We demonstrated that not only do the cancer stem cells have elevated ALDH1A1 activity in cell culture, but they maintain elevated activity through establishment of a tumor microenvironment. We next sought to improve on certain limitations of AlDeSense, namely the green fluorescence and cell impermeability. Towards this goal, eleven possible Si-xanthene probes were synthesized. Each iteration provided new insights into the electronic and steric requirements for isoform selectivity and fluorescence turn on. In the end, the careful incorporation of two fluorine atoms on the reactive b…
abstract: Molecular imaging agents are chemical tools that have become essential to the study of life. The field of molecular imaging encompasses a wide range of modalities and mechanism, but an exciting and growing subfield is that of activity-based sensing. Activity-based sensors provides new insights into biological processes since they report on the activity of biological species rather than just the presence. Naturally these are ideal probes for enzymes, affording multiple turnovers and higher signal from a single active enzyme. Activity-based sensors are also excellent sensors for reactive small molecules with unique chemical reactivity. Here, we report the development and/or progress on activity-based sensors for reactive biological aldehydes and the enzymatic machinery tasked with aldehyde metabolism. We first developed AlDeSense, the first turn on fluorescent probe selective for aldehyde dehydrogenase (ALDH) 1A1. We pursued a probe for this enzyme since it’s frequently cited as a cancer stem cell marker. AlDeSense had remarkable selectivity for ALDH1A1, producing a 20-fold increase in fluorescence signal upon oxidation by the enzyme. We confirmed ALDH1A1 activity, as measured by AlDeSense, was a reliable cancer stem cell marker in leukemia, melanoma, and breast cancer models. AlDeSense was then applied to image ALDH1A1 activity in aggressive and non-aggressive melanoma ex vivo and in vivo. We demonstrated that not only do the cancer stem cells have elevated ALDH1A1 activity in cell culture, but they maintain elevated activity through establishment of a tumor microenvironment. We next sought to improve on certain limitations of AlDeSense, namely the green fluorescence and cell impermeability. Towards this goal, eleven possible Si-xanthene probes were synthesized. Each iteration provided new insights into the electronic and steric requirements for isoform selectivity and fluorescence turn on. In the end, the careful incorporation of two fluorine atoms on the reactive b…
author: Bearrood, Thomas Edward
language: en
keywords: molecular imaging, activity-based sensors, aldehydes, aldehyde dehydrogenase, 4-hydroxynonenal
date published: 2020-12
date modified: 2026-07-22T22:24:50Z
provider: University of Illinois - Urbana-Champaign
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Illinois at Urbana-Champaign

PropertyValue
property ID: Handle
value: http://hdl.handle.net/2142/109493