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Bifacial Peptide Nucleic Acid (bPNA) as a Regulator of Nucleic Acid Function

Xia, Xin
http://rave.ohiolink.edu/etdc/view?acc_num=osu1437506395

Abstract Details

2015, Doctor of Philosophy, Ohio State University, Chemistry.
This dissertation contains research summaries regarding the characterizations and applications of a novel bifacial peptide nucleic acid (bPNA) triplex system. The main content is divided into two parts: part one (chapter 2) presents systematic studies on effective in vitro inhibition of transcription, reverse-transcription and exonuclease function via the formation of synthetic bPNA-nucleic acid triplex structures; part two (chapters 3 and 4) demonstrates that bPNA triplex hybrid functionally substitutes for native duplex structures that are crucial for proper functions of aptamers and ribozyme, further a two-way communication system describing RNA-templated oxidative coupling of bPNA fragments leads to the emergence of ribozyme cleavage is discussed in details. In part one, we speculate that the thermodynamically stable synthetic bPNA-nucleic acid triplex can be utilized to generate template distortions that are inhibitory to nucleic acid based enzymatic reactions. Three enzymatic systems were investigated: T7 RNA polymerase, Exonuclease T, and AMV reverse transcriptase. bPNA hybridization kinetics and inhibitory efficacies on each system will be discussed in detail in chapter 2. In part two, study on bPNA-nucleic acid triplex system was expanded to investigate the structure-function relation of nucleic acid. In chapter 3, three biologically active nucleic acids folds were selected: IgE DNA aptamer, spinach RNA aptamer and minimal type I hammerhead ribozyme. Replacement of a duplex stem with unstructured oligo-T/U strands, which are bPNA binding sites, imposed structure-function loss in all three nucleic acids folds. Functional rescue was observed upon bPNA-driven refolding of oligo-T/U strands into triplex hybrid system. Further, in chapter 4, we demonstrated a 2-way communication between the abiotic bPNA hybridization site and the native ribozyme cleavage site, where the ribozyme-templated bPNA ligation in turn restore the ribozyme self-cleavage activity. In summation, we will demonstrate to you that bPNA triplex stem structure is compatible with biological processes and presented to be competitive inhibitor for DNA/RNA specific enzymes; further, bPNA triplex stem is biologically similar to native stem structures, not only the bPNA hybridization but also the nucleic acid templated bPNA ligation can restore native nucleic acid activities, demonstrate readout and transformation of non-native macromolecules through an abiotic template interface in DNA/RNA template topologies that are not accessible via native base-pairing.
Bong Dennis (Advisor)
Karin Musier-Forsyth (Committee Member)
Kotaro Nakanishi (Committee Member)
315 p.
Chemistry

Recommended Citations

Citations

  • Xia, X. (2015). Bifacial Peptide Nucleic Acid (bPNA) as a Regulator of Nucleic Acid Function [Doctoral dissertation, Ohio State University]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=osu1437506395

    APA Style (7th edition)

  • Xia, Xin. Bifacial Peptide Nucleic Acid (bPNA) as a Regulator of Nucleic Acid Function. 2015. Ohio State University, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=osu1437506395.

    MLA Style (8th edition)

  • Xia, Xin. "Bifacial Peptide Nucleic Acid (bPNA) as a Regulator of Nucleic Acid Function." Doctoral dissertation, Ohio State University, 2015. http://rave.ohiolink.edu/etdc/view?acc_num=osu1437506395

    Chicago Manual of Style (17th edition)

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This open access ETD is published by The Ohio State University and OhioLINK.