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Full-Text Articles in Biochemistry
Termination-Independent Role Of Rat1 In Cotranscriptional Splicing In Budding Yeast, Zuzer Hakimuddin Dhoondia
Termination-Independent Role Of Rat1 In Cotranscriptional Splicing In Budding Yeast, Zuzer Hakimuddin Dhoondia
Wayne State University Dissertations
Rat1 is a 5′→3′ exoribonuclease in budding yeast belonging to the XRN-family of nucleases. It is a highly conserved protein with homologs being present in fission yeast, flies, worms, mice and humans. Rat1 and its homolog in metazoan have been shown to function in multiple facets of RNA metabolism. In this study, we report a novel role of Rat1 in splicing of pre-mRNA in budding yeast. In the absence of the functional Rat1 in the nucleus, an increase in the level of unspliced transcripts was observed in yeast cells. Strand-specific TRO analysis revealed that the accumulation of unspliced transcripts upon …
Insights Into Nucleic Acid-Platinum(Ii) Compound Interactions And Structural Impacts, Supuni Duneeshya Kamal Thalalla Gamage
Insights Into Nucleic Acid-Platinum(Ii) Compound Interactions And Structural Impacts, Supuni Duneeshya Kamal Thalalla Gamage
Wayne State University Dissertations
With the discovery of cisplatin in the 1960s, it has been widely studied as a precursor for anticancer drug development. Despite its effectiveness against certain cancers, clinical usage of cisplatin is restricted by a number of side effects and resistance. In the past decade, scientists have been exploring biologically important ligands such as sugar derivatives in the hope of overcoming such challenges. Attachment of a sugar moiety could facilitate lower accumulation of platinum drugs in the body as well as enhance cellular uptake. In this study, a carbohydrate-linked cisplatin analog, cis-dichlorido[(2-β-D-glucopyranosidyl)propane-1,3-diammine]platinum (5) has been studied. The aim was to evaluate …
The Development Of Peptide Ligands To Target H69 Rrna, Danielle Nicole Dremann
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 …
Platination Kinetics: Insight Into Rna-Cisplatin Interactions As A Probe For Rna Microenvironments, Gayani Dedduwa-Mudalige
Platination Kinetics: Insight Into Rna-Cisplatin Interactions As A Probe For Rna Microenvironments, Gayani Dedduwa-Mudalige
Wayne State University Dissertations
RNAs are crucial for many cellular functions. Thus, studying ligand-RNA interactions and their dynamics in response to changes in the surrounding environment is important. In spite of the well-known DNA coordination, current research also indicates cisplatin binding to RNA. Kinetic studies of rRNA platination reactions are largely unexplored. This research was conducted to achieve two objectives. First, a broad kinetic study was carried out to investigate the cisplatin-rRNA interactions. The structure, function, and ligand interactions depend on RNA microenvironments. Second, the application of platination kinetics as a tool to interrogate RNA electrostatic environments was explored.
Three model rRNA hairpins from …