Identification and investigation of RNA-binding ligands

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Chemistry

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2013

Author dc:creator

• Richardson, Stacie

Contributors dc:contributor

• Baranger, Anne M.
• Zimmerman, Steven C.
• Katzenellenbogen, John A.
• van der Donk, Wilfred A.

• RNA
• Ligand
• MBNL1
• myotonic dystrophy
• trinucleotide repeats
• CUG repeats

Statement dc:rights

• Copyright 2012 Stacie Richardson

Language dc:language

en

Handle dc:identifier

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

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/42196