University of Illinois Urbana-Champaign

DNA-catalyzed covalent modification of amino acid side chains in tethered and free peptide substrates

Wong, On Yi

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Wong_OnYi.pdf

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https://hdl.handle.net/2142/29668

Description

Title
DNA-catalyzed covalent modification of amino acid side chains in tethered and free peptide substrates
Author(s)
Wong, On Yi
Issue Date
2012-02-06T20:09:58Z
Director of Research (if dissertation) or Advisor (if thesis)
Silverman, Scott K.
Committee Member(s)
  • Bailey, Ryan C.
  • Hergenrother, Paul J.
  • Martinis, Susan A.
Department of Study
Chemistry
Discipline
Chemistry
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Date of Ingest
2012-02-06T20:09:58Z
Keyword(s)
  • Deoxyribozymes
  • amino acid side chains modifications
Abstract
Scientists thought of RNA as passive messenger molecules until the discovery of catalytic RNA (ribozymes) in the 1980s, which revolutionized thinking toward the multifaceted functions of RNA. The discovery of catalytic RNA also sparked an intense interest in exploring the catalytic functions of nucleic acids. As a close analog of RNA, the catalytic ability of DNA was evaluated and the first artificial DNA catalyst (deoxyribozyme) discovered in 1994. Since then, deoxyribozymes have been shown to catalyze a wide variety of chemical reactions, including phosphodiester bond cleavage, nucleic acid ligation, thymine dimer photoreversion, and the Diels-Alder reaction. However, the majority of deoxyribozyme-catalyzed reactions involve oligonucleotide substrates. To expand the scope of substrates that can be catalyzed by deoxyribozymes, the main theme of the thesis is to seek DNA catalysts that covalently modify the side chains of amino acids. The thesis describes the numerous selection efforts that led to the first discovery of a particular deoxyribozyme to catalyze the reactivity of a free tripeptide. This unprecedented discovery establishes a future potential use of DNA to modify proteins. In addition, this thesis presents the unexpected discovery of DNA-catalyzed reductive amination that may be applicable to site-specific labeling of nucleic acids. Finally, the thesis summarizes the optimization of the incubation conditions using click chemistry for direct free peptide selection. From these studies, we gained insights on how to direct our future selection efforts to identify DNA-catalyzed reactivity of amino acid side chains.
Graduation Semester
2011-12
Permalink
http://hdl.handle.net/2142/29668
Copyright and License Information
Copyright 2011 On Yi Wong

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