Identification and investigation of RNA-binding ligands

Richardson, Stacie

Permalink

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

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

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

Owning Collections