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Characterization Of Protonated Modified Nucleosides And Amino Acid-Linked Cisplatin Analogues Using Tandem Mass Spectrometry Complemented By Theoreticical Approaches, Chenchen He

Wayne State University Dissertations

The chemical difference between DNA and RNA nucleosides is their 2′-hydrogen versus 2′-hydroxyl substituents. The 2′-O-methylation is common among natural posttranscriptional modifications of RNA. The structures and relative glycosidic bond stabilities of the protonated forms of the 2′-O-methylated nucleosides, 2′-O-methyladenosine (Adom), 2′-O-methylguanosine (Guom), 2′-O-methycytidine (Cydm), 2′-O-methyluridine (Urdm), and 5,2′-O-dimethyluridine (Thdm) are examined using two complementary tandem mass spectrometry approaches, infrared multiple photon dissociation (IRMPD) action spectroscopy and energy-resolved collision-induced dissociation (ER-CID). Theoretical calculations are also performed to predict the structures and relative stabilities of stable low-energy conformations of the protonated forms of the 2′-O-methylated nucleosides and their infrared spectra in …

The Development Of Peptide Ligands To Target H69 Rrna, Danielle Nicole Dremann

Wayne State University Dissertations

ABSTRACT

THE DEVELOPMENT OF PEPTIDE LIGANDS TO TARGET H69

by

DANIELLE NICOLE DREMANN

December 2015

Advisor: Prof. Christine S. Chow

Major: Chemistry (Biochemistry)

Degree: Doctor of Philosophy

In the development of peptide ligands to target H69, SPPS and ESI MS was used to determine if 1) peptides could bind to modified H69 and 2) if increased affinity for the target RNA could be enhanced with modification. An alanine and arginine scan was synthesized and tested for this determination. Selected peptides were then tested using biophysical techniques such as circular dichroism and isothermal titration calorimetry. An assay was also designed to …

Synthesis, Characterization, And Rna Reactivity Of Amino-Acid-Linked Cisplatin Analogues, Xun Bao

Wayne State University Dissertations

The essential role of ribosomal RNA (rRNA) in the cell life cycle is highlighted by protein synthesis; therefore, the ribosome is considered to be an ideal drug target. Ribosomal RNAs exhibit a high level of structural diversity. The well-known anticancer drug cisplatin was previously applied as a chemical probe of rRNA structure to determine solvent accessible purines (guanosine) in vivo and in vitro. Cisplatin accumulates faster on RNA than DNA, with less chance of repair. As such, designing new RNA-targeting Pt compounds is not only a promising direction for chemical-probing applications, but also for the design of anticancer drugs that …

Development Of Inlet And Vacuum Ionization Methods For Characterization Of Biological Materials By Mass Spectrometry, Beixi Wang

Wayne State University Dissertations

Inlet ionization and vacuum ionization are novel ionization methods to produce electrospray ionization (ESI)-like ions from the solid or liquid states, operating from atmospheric pressure (AP) or vacuum, without the use of voltage or the necessity of high energy input such as a laser or particle beam. The fundamental aspects were probed for better understanding of the novel ionization processes. Initial applications were attempted to utilize the novel ionization methods for fast, robust, and quantitative analyses.

For inlet ionizations (laserspray ionization inlet, LSII; matrix assisted ionization inlet, MAII; and solvent assisted ionization inlet, SAII), small (e.g. drugs) to large (e.g. …