Modified nucleotides and nucleic acids as molecular probes
Abstract/Contents
- Abstract
- This thesis discusses a number of projects involving the use of modified nucleotides and oligonucleotides in addressing some basic science questions and some clinical and technological applications.The first chapter details our efforts at using telomere-encoding circular DNA in elongating zebrafish telomeres. We microinjected our synthetic circular DNA into zebrafish embryos and studied their telomere length 24 hrs later. Using Quantitative Fluorescence in situ Hybridization (Q-FISH) as the analytical tool to determine telomere length, we observed no significant difference in telomere length between the group injected with the synthetic DNA and the control group. In the second chapter we studied the potential of a non-polar shape mimic of iodo-uracil as an imager of tumors. We continued discussing our work with non-polar nucleotide isosteres in the third chapter where we used them in investigating a novel active site in polymerase from Pyrococcus furiosus (Pfu). From our studies we concluded that although shape was an important factor in distinguishing bases, this binding site also employed hydrogen bonding to identify nucleoabases. The lack of any recognition of the syn-oxidized bases suggested that the enzyme preferred to recognize bases in the anti conformation rather than syn. In the fourth chapter we were interested in understanding the factors determining the fidelity and selectivity observed in RNA Polymerase II mediated transcription. Once again we used non-polar shape mimics of thymidine (dF) and adenine (dQ) to study the importance of shape and hydrogen bonding. We observed that the thymidine mimic was recognized better by the RNA Polymerase II active site than the mis-match bases. The adenine isostere on the other hand, was poorly recognized. This preliminary study demonstrates the importance of both shape and hydrogen bonding. The last chapter discusses our studies using polyfluorophores on a DNA backbone to detect gases. Following a combinatorial method, a library of oligodeoxyfluorosides (ODFs) were synthesized from which sensors of gases were selected. Using this method we were able to select optical sensors for a diverse set of small molecules in vapor state.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2010 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Ghosh, Samantak | |
|---|---|---|
| Associated with | Stanford University, Department of Chemistry | |
| Primary advisor | Kool, Eric T | |
| Thesis advisor | Kool, Eric T | |
| Thesis advisor | Chen, James Kenneth | |
| Thesis advisor | Huestis, Wray | |
| Advisor | Chen, James Kenneth | |
| Advisor | Huestis, Wray |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Samantak Ghosh. |
|---|---|
| Note | Submitted to the Department of Chemistry. |
| Thesis | Thesis (Ph. D.)--Stanford University, 2010. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2010 by Samantak Ghosh
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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