Lead compound discovery for myotonic dystrophy

Ho, Yen-Jun

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https://hdl.handle.net/2142/46951 Copy

Description

Title

Lead compound discovery for myotonic dystrophy

Author(s)

Ho, Yen-Jun

Issue Date

2013-06-03

Director of Research (if dissertation) or Advisor (if thesis)

Zimmerman, Steven C.

Department of Study

Chemistry

Discipline

Chemistry

Degree Granting Institution

University of Illinois at Urbana-Champaign

Degree Name

M.S.

Degree Level

Thesis

Keyword(s)

• myotonic dystrophy
• small molecules
• fluorescence anisotropy
• high-throughput screen
• RNA targeting
• MBNL1
• CUG repeats

Abstract

Myotonic dystrophy is a debilitating genetic disorder which currently does not have a therapeutic treatment. It is understood that CTG expansions lead to formation of stable poly(CUG) mRNA which mislocalize splicing factors such as MBNL1 and lead to missplicing in the cell. One therapeutic strategy is to target such mutant mRNA with small molecules to prevent the sequestration of splicing factors which will prevent the multiple missplicing events in the cell and rescue the symptoms of the disorder. In the following thesis I describe my work in identifying small molecule inhibitors of the RNA-protein complex through the optimization of gel shift assays for characterization of rationally-designed compounds and the development of a fluorescence anisotropy assay for a high-throughput screening of the NCI Diversity Set III compound library. From such studies I was able to identify several lead compounds that are successful at inhibiting the pathological nuclear aggregation.

Graduation Semester

2013-05

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http://hdl.handle.net/2142/46951

Copyright and License Information

Copyright 2013 Yen-Jun Ho

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