Development of fluorescent chemical biology tools for the detection and delivery of aldehyde-associated biology

Pino, Nicholas W.

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https://hdl.handle.net/2142/115368 Copy

Description

Title

Development of fluorescent chemical biology tools for the detection and delivery of aldehyde-associated biology

Author(s)

Pino, Nicholas W.

Issue Date

2022-04-20

Director of Research (if dissertation) or Advisor (if thesis)

Chan, Jefferson K

Doctoral Committee Chair(s)

Chan, Jefferson K

Committee Member(s)

• Hergenrother, Paul J
• van der Donk, Wilfred A
• Lu, Yi

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

Ph.D.

Degree Level

Dissertation

Keyword(s)

• Fluorescence
• chemical biology, aldehydes
• HNO

Abstract

Small molecules in biology have been studied by chemists and biologists for decades. As we have grown to understand more, we have discovered that highly reactive and difficult to analyze small molecules can be involved in far more biological processes than we previously believed. Aldehydes are one class of these small molecules. While it was previously believed that aldehydes were simply toxic compounds that could be used for embalming (i.e. formaldehyde) or inconsequential metabolites (e.g. acetaldehyde), research into these aldehydes and hundreds of others has lead us to understand that aldehydes play important roles in native mammalian biology. As analytical methods have reach their limits in biological study of aldehydes, we as chemical biologists have taken note of areas in which we could drive aldehyde-related research into the future with molecular tools assisted by fluorescence. Herein, we report of the development of tools that address different aspects of aldehyde-related biology including detection of aldehyde related enzymes, presence of inhibitors of these enzymes, and quantitative delivery of aldehydes to living cells. Our strategy for devising chemical biology tools is rooted deeply in physical organic chemistry. In each case, a selective sensing or delivery strategy is devised and optimized on the principles of physical organic phenomena which gives us high confidence in the output results that our tools provide. Specifically, we have developed fluorescent sensors for aldehyde dehydrogenase 1A1 (ALDH1A1) and nitroxyl (HNO) a reactive nitrogen species that reacts with aldehyde dehydrogenase 2 (ALDH2) to inhibit aldehyde oxidation. We also developed a donor of formaldehyde whose fluorescent readout can be leveraged for quantification of aldehyde release in cells.

Graduation Semester

2022-05

Type of Resource

Thesis

Copyright and License Information

Copyright 2022 Nicholas Pino

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