Part I: development and applications of oligodeoxyfluorosides as metal ion sensor array; part II: fluorogenic darkzone dyes for in vitro and intracellular aldehyde labeling
Abstract/Contents
- Abstract
- This thesis consists of two parts. Part I discusses the synthesis and applications of fluorescent DNA-based chemosensors on beads to detect and differentiate metal ions in water. Four fluorescent deoxyribosides were designed and synthesized as varied metal binding ligands. Combined with other deoxyribosides, a tetramer-length oligodeoxyfluoroside (ODF) library of 6561 members was constructed and screened for sequences responsive to metal ions. Screening of the ODF library yielded ODF sequences that respond to 37 metal ions within an hour. Seven strongly-responding sequences were selected as a sensor array and used to detect eight metal environmental contaminants in deionized water and in a contaminated California surface water sample at low micromolar range. Statistical analysis of the response patterns showed successful differentiation of the eight analytes in deionized water at concentrations as low as 100 nM in deionized water and surface water. The potential of the ODF metal ion sensor array was further explored by simultaneously discriminating 57 metals, including alkali, alkaline earth, post-transition, transition and lanthanide metals, with only nine sensors, demonstrating the ability of sensor array to detect and differentiate a large number of analytes with few sensors. As few as six ODF chemosensors can detect and differentiate 50 metals at 100 µM, and a blind test with 50 metals further confirmed the discriminating power of the ODFs. The ODF design described here demonstrates the potential of ODF sensor array as a convenient and inexpensive tool for environmental contaminant sensing. Part II of this thesis describes the design and development of a fluorogenic aldehyde labeling reagent using hydrazone exchange. This quenched hydrazone or DarkZone system adopts a previously unknown aldehyde dependent hydrazone exchange mechanism. Organocatalysts for hydrazone formation were found to accelerate DarkZone labeling, with at least two showing biocompatibility. The multi-color DarkZone dyes can label peptide in vitro and small aliphatic aldehydes and endogenously produced acetaldehyde in a cellular environment, demonstrating the versatility of the DarkZone dyes as a research and diagnostic tool.
Description
| Alternative title | Development and applications of oligodeoxyfluorosides as metal ion sensor array |
|---|---|
| Alternative title | Fluorogenic darkzone dyes for in vitro and intracellular aldehyde labeling |
| Type of resource | text |
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2016 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Yuen, Lik Hang |
|---|---|
| Associated with | Stanford University, Department of Chemistry. |
| Primary advisor | Kool, Eric T |
| Thesis advisor | Kool, Eric T |
| Thesis advisor | Cegelski, Lynette |
| Thesis advisor | Kanan, Matthew William, 1978- |
| Advisor | Cegelski, Lynette |
| Advisor | Kanan, Matthew William, 1978- |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Lik Hang Yuen. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2016. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2016 by Lik Hang Yuen
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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