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Synthesis and Characterization of Modified Polyadenosines for Applications as a pH-Responsive Nanodevice


Synthesis and Characterization of Modified Polyadenosines for Applications as a pH-Responsive Nanodevice

Duke, Kieran (2021) Synthesis and Characterization of Modified Polyadenosines for Applications as a pH-Responsive Nanodevice. Masters thesis, Concordia University.

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The need for structurally and functionally diverse nanomaterials is rapidly expanding with increasing applications in various fields including medicine and biotechnology. RNA has been gaining recognition as a nanomaterial due to its ability to engage in both Watson-Crick and non-canonical interactions as well as its capacity to adopt structural motifs distinct from those of DNA. One such structure, the poly(A) RNA duplex, first described by Rich et al in 1961, is parallel-stranded and stabilised by hydrogen bonds between the Hoogsteen edges of the adenine bases. Acidic conditions or ammonium (NH4+) promotes duplex formation. Poly(A) RNA lends itself for applications as a pH-responsive nanomaterial similar to other nucleic acid structures including the i-motif.
The aim of this thesis was to expand upon previous studies that investigated the influence of 2'-modifications on the poly(A) RNA duplex. Here, the effects of 2'-O-propargyl functionality, and additional Click chemistry derivatization employing copper(I)-catalyzed azide-alkyne cycloaddition was explored to assess relationships between structure and stability.
Incorporation of the 2'-O-propargyl functionality was found to be destabilizing towards duplex formation. Click chemistry derivatization was performed with small molecule azides including 4-azidobutylamine and 1-(azidomethyl)pyrene. Duplexes that incorporated the amine functionality through the 1,4-triazole linkage were found to be destabilized, where as, pyrene modifications provided stabilization upon successive incorporations. Fluorescence analysis of pyrene-functionalized oligonucleotides provided insight into the localization of the pyrene group and potential flexibility differences between the ends of the duplex. These findings will guide the design of future duplex modifications to enhance its’ application as a pH-responsive nanomaterial.

Divisions:Concordia University > Faculty of Arts and Science > Chemistry and Biochemistry
Item Type:Thesis (Masters)
Authors:Duke, Kieran
Institution:Concordia University
Degree Name:M. Sc.
Date:26 July 2021
Thesis Supervisor(s):Wilds, Christopher
Keywords:Nucleic acids, RNA, pH-Responsive, Nanomaterials, poly(A) duplex.
ID Code:988904
Deposited By: KIERAN DUKE
Deposited On:29 Nov 2021 16:41
Last Modified:01 Sep 2022 00:00


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