Synthesis of a modified analog of uridine and the study of small-molecule interactions with RNA
Abstract
There are over 100 different natural nucleic acid modifications in nature. These modifications have different functions to serve their purpose and dictate the RNA secondary and tertiary structural motifs. One of the modifications, pseudouridine, will be discussed in Chapter 1. Pseudouridine has been found in areas of functional importance. One particular area that contains a modification of pseudouridine, 1-methyl-3-(3-amino-3-carboxypropyl)pseudouridine (m 1 acp3 Ψ), is the loop region of RNA hairpin helix 31 (H31) of both E. coli and H. sapiens. H31 is known to contact the decoding region; this modified pseudouridine may play a significant role. Chapter 2 will discuss synthesis of a uridine analog, N 3-(5-amino-5-carboxypentanyl)uridine (acp5 U). The amino-acid side chain presents new opportunities to study the effects of modification on nucleoside conformation in solution. The structure and conformation of acp5 U was determined using 2D NMR and 1D NOE difference spectroscopy. Circular dichroism (CD) spectroscopy was also used to study the conformation of the uridine analogue and compare to related uridine derivatives. In recent years, binding studies of small molecules with RNA have been widely explored. There are many known ligands such as aminoglycosides that bind to RNAs to either enhance or destroy the RNA functions or structures. Small peptide molecules have been selected against target RNAs of interest and synthesized for the purpose of this study. In the second part of this thesis work, electrospray ionization mass spectrometry (ESI-MS) was utilized to study small molecule (peptide) interactions with RNA. These studies are presented in Chapter 3.
Recommended Citation
Tony Huei-Hong Wang,
"Synthesis of a modified analog of uridine and the study of small-molecule interactions with RNA"
(January 1, 2007).
ETD Collection for Wayne State University.
Paper AAI1451071.
http://digitalcommons.wayne.edu/dissertations/AAI1451071
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