Towards the Therapies of Tomorrow: Selective RNA Binding Small Molecules and Cytoprotective Strategies for Ros-Mediated Disease States

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.

Name thesis:degree_name

Ph.D.

Level thesis:degree_level

Dissertation

Discipline thesis:degree_discipline

Biophysics and Computational Biology

Grantor

University of Illinois at Urbana-Champaign

Year dc:date

2015

Author dc:creator

• Thomas, Jason Ray

Contributors dc:contributor

• Hergenrother, Paul J.

• Biophysics, General

Language dc:language

eng

Identifier

(MiAaPQ)AAI3290400

OAI identifier oai:identifier

oai:www.ideals.illinois.edu:2142/85462