University of Illinois Urbana-Champaign

Identification and investigation of RNA-binding ligands

Richardson, Stacie

Content Files
Stacie_Richardson.pdf

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https://hdl.handle.net/2142/42196

Description

Title
Identification and investigation of RNA-binding ligands
Author(s)
Richardson, Stacie
Issue Date
2013-02-03T19:27:34Z
Director of Research (if dissertation) or Advisor (if thesis)
Baranger, Anne M.
Doctoral Committee Chair(s)
Baranger, Anne M.
Committee Member(s)
  • Zimmerman, Steven C.
  • Katzenellenbogen, John A.
  • van der Donk, Wilfred 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
2013-02-03T19:27:34Z
Keyword(s)
  • RNA
  • Ligand
  • MBNL1
  • myotonic dystrophy
  • trinucleotide repeats
  • CUG repeats
Abstract
Myotonic dystrophy type 1 is caused by a toxic CUG RNA repeat expansion in the 3’-UTR of the DMPK gene that sequesters a key splicing regulator, MBNL1, preventing normal modulation of alternative splicing of a variety of genes. Targeting these repeats with small molecules could block the sequestration of MBNL1 and restore normal splicing levels, alleviating the pathogenesis of the disease. To that end, I have screened a library of select compounds, chosen for their potential to act as RNA binding ligands. From the initial screen, I identified several promising lead compounds. I proceeded to perform a structure-activity relationship (SAR) study on one of the lead molecules, NSC657704. Based on the results of the SAR, I designed a set of derivatives, synthesized them, and ascertained their inhibitory activity and RNA binding affinity.
Graduation Semester
2012-12
Permalink
http://hdl.handle.net/2142/42196
Copyright and License Information
Copyright 2012 Stacie Richardson

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