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Development of Thioamides as Protein Probes / Daniel Miklos Szantai-Kis.
- Format:
- Book
- Thesis/Dissertation
- Author/Creator:
- Szantai-Kis, Daniel Miklos, author.
- Language:
- English
- Subjects (All):
- Cellular biology.
- Biochemistry.
- Organic chemistry.
- Biochemistry and Molecular Biophysics--Penn dissertations.
- Penn dissertations--Biochemistry and Molecular Biophysics.
- Local Subjects:
- Cellular biology.
- Biochemistry.
- Organic chemistry.
- Biochemistry and Molecular Biophysics--Penn dissertations.
- Penn dissertations--Biochemistry and Molecular Biophysics.
- Genre:
- Academic theses.
- Physical Description:
- 1 online resource (246 pages)
- Contained In:
- Dissertations Abstracts International 81-04B.
- Place of Publication:
- [Philadelphia, Pennsylvania] : University of Pennsylvania ; Ann Arbor : ProQuest Dissertations & Theses, 2019.
- Language Note:
- English
- System Details:
- Mode of access: World Wide Web.
- text file
- Summary:
- Thioamides have been used for various applications with small molecules and peptides, including as protease sensors, fluorescence quenching probes, folding probes, and handles for site-specific chemical modification. However, their use in proteins has been limited due to cumbersome incorporation through semi-synthesis, as well as their unknown effects on protein structure. In this work, I address these issues from multiple perspectives. I present improvements for the synthesis of thioamide-containing peptides, which are needed for semi-synthesis. I also investigate the effects that thioamide substitutions have on tertiary structure in a model protein and show that based on thermal denaturation experiments, the position of thioamide substitution can have a significant impact on the tertiary fold. Furthermore, I demonstrate a new semi-synthetic strategy to obtain mg quantities of a thioamide-containing protein that will enable structural investigation by Nuclear Magnetic Resonance spectroscopy and X-Ray crystallography. Finally, I describe my attempts at the genetic incorporation of thioamides using a combination of unnatural amino acid mutagenesis and amber suppression. While the last part was not successful, the efforts to improve semi-synthesis of thioamides will enable the use of thioamides as probes in proteins in a similar fashion as they have been used previously in peptides.
- Notes:
- Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
- Advisors: Petersson, Ernest J; Committee members: Yale Goldman; Carol Deutsch; David Chenoweth; Kathleen Howard.
- Department: Biochemistry and Molecular Biophysics.
- Ph.D. University of Pennsylvania 2019.
- Local Notes:
- School code: 0175
- ISBN:
- 9781392786178
- Access Restriction:
- Restricted for use by site license.
- This item is not available from ProQuest Dissertations & Theses.
- This item must not be sold to any third party vendors.
- This item must not be added to any third party search indexes.
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