Towards the Therapies of Tomorrow: Selective RNA Binding Small Molecules and Cytoprotective Strategies for Ros-Mediated Disease States
Thomas, Jason Ray
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https://hdl.handle.net/2142/85462
Description
Title
Towards the Therapies of Tomorrow: Selective RNA Binding Small Molecules and Cytoprotective Strategies for Ros-Mediated Disease States
Author(s)
Thomas, Jason Ray
Issue Date
2007
Doctoral Committee Chair(s)
Hergenrother, Paul J.
Department of Study
Biophysics and Computational Biology
Discipline
Biophysics and Computational Biology
Degree Granting Institution
University of Illinois at Urbana-Champaign
Degree Name
Ph.D.
Degree Level
Dissertation
Keyword(s)
Biophysics, General
Language
eng
Abstract
There is a growing appreciation for the dynamic and regulatory roles which RNA plays in the cell. Growing along this appreciation is the notion of targeting RNA as a potential medicinal strategy. A small molecule that is able to selectively bind one mRNA from the entire transcriptome would specifically prevent the translation of the target protein. However, current classes of small molecules used to bind RNA are of mediocre affinity and generally lack specificity. Our ultimate goal is to develop a paradigm for targeting any RNA within a cell based upon its secondary structure, which can be predicted with reliable accuracy from its primary sequence. It is proposed that small molecules can be developed to selectively bind the distinguishing features of RNA, namely hairpin loop, bulged, and internal loop regions. Linking of modules via a tether of defined length and composition will lead to specificity by restricting the number of targetable RNAs. In order to obtain such modules, principles of molecular recognition have been applied to scaffolds of unique geometries that have a demonstrated propensity to bind nucleic acids with secondary structure-specificity. Once modules have been developed, sequence specificity with each class of secondary structures can be obtained by the functionalization of the modules, thus creating modules within modules.
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