Date of Award

1-1-2012

Language

English

Document Type

Master's Thesis

Degree Name

Master of Science (MS)

College/School/Department

Department of Chemistry

Content Description

1 online resource (v, 50 pages) : illustrations (some color)

Dissertation/Thesis Chair

Li Niu

Committee Members

Pan Li

Keywords

aptamers, RNA, Oligonucleotides, Neurotransmitter receptors

Subject Categories

Chemistry | Molecular Biology

Abstract

The relationship of excessive activity of AMPA-type glutamate receptors, and cell death, has long provided researchers a means of investigating neurodegenerative disorders, such as Parkinson's Disease (PD) and amyotrophic lateral sclerosis (ALS). Inhibitors of AMPA receptor channels, including chemical and nucleic acid molecules such as RNA aptamers, have served as potential therapeutic agents and treatment of neurodegenerative disorders. In this study, building bipartite aptamers to enhance inhibitory potency, as compared with a monomeric aptamer of AMPA receptor, is described. An enhanced potency is due, at least in part; to the proximity effect in bipartite structures or binding of a monomeric unit to the receptor site enhances the binding of another monomeric unit, in close proximity, to another target site on the receptor, therefore enhancing potency. Specifically in this study, a known aptamer of AMPA receptor was used to design four different bipartite structures, with different 3'-end joining tails, whose biological activities were assayed with the GluA2Qflip AMPA receptor expressed in HEK-293 cells using whole-cell recording. However, in each structure, there was no substantial increase in potency as compared to the single, monomeric aptamer. Despite the indifference of the reported results, several conclusions and implications can be drawn for future investigation. Those implications include ways to design different 3'-end joining tails for bipartite aptamer assembly and to construct RNA structures in a more predictable fashion without affecting the functionality of the monomeric aptamer activity.

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