Chemistry Commons^™

Study Of Protein-Rna Interactions Using Fluorescence Resonance Energy Transfer (Fret) And Single-Molecule Fret, Rajan Lamichhane

Wayne State University Dissertations

In the cell, RNA and protein, interact to form ribonucleoprotein complexes (RNPs) that have vital structural, catalytic and regulatory roles. Despite their functional importance, the mechanistic details and dynamics of RNPs are poorly understood. Single-molecule Fluorescence Resonance Energy Transfer (smFRET) techniques that provide information about heterogeneity and dynamic behaviors of molecules have been developed to investigate inter- and intra-molecular interactions. Here we have used FRET in combination with smFRET to study three very different RNP systems.

Alternative splicing is a highly regulated biological process that plays a crucial role in proteomic diversity in eukaryotes. One splicing regulator, PTB, has been …

Chemical Synthesis Of Peptides And Peptide Thioesters, Indrajeet Sharma

Wayne State University Dissertations

This dissertation describes investigations toward the development of a new chemistry for the block synthesis of peptides and peptidyl thioesters. A direct approach for the Fmoc-SPPS of peptidyl thioesters is also delineated in this thesis.

In the first part of chapter one, the difficulty and importance of chemical synthesis of peptides is explained, and a brief survey of available methods is given. The second part of chapter one presents the challenges inherent in the synthesis of peptidyl thioesters by Fmoc-SPPS.

The second chapter outlines the investigations conducted towards the development of a new chemistry for epimerization-free block synthesis of peptides …

Electronic Excitations In Branched Conjugated Oligomers: A Quasiparticle View And Tight-Binding Models, Hao Li

Wayne State University Dissertations

This dissertation focuses on the theoretical understanding and simulation of the excited state electronic structures of organic conjugated molecules. The exciton scattering (ES) approach has been extended for efficient calculation of optical spectra of large branched conjugated oligomers. The methodology of tight-binding (lattice) model, originally developed in condensed matter theory, has been extended to the building block structure of conjugated molecules for explicit description of the electronic excitations.

Within the ES approach, the electronic excitations in quasi-1D molecular structures are attributed to standing waves that represent quantum quasiparticles (excitons) scattered at the molecular vertices. Excitation energies can be found by …

Synthesis Of Peptide-Ligand Conjugates And Their Applications, Nitinkumar Dilipkumar Jabre

Wayne State University Dissertations

Three research areas pertaining to this dissertation, (i) synthesis strategies of peptide-ligand conjugates, (ii) their applications and (iii) chemistry of ferryls were surveyed in the introduction chapter. Next, the divergent and dual divergent strategies for the synthesis of non-heme ligand-peptide conjugates were developed. Using these strategies various peptide-ligand conjugates were synthesized via solution as well as solid phase synthesis. The scope and the functional group compatibility of these strategies were also established. The utility of the dual divergent strategy has been demonstrated by synthesizing a small library of metal-binding LHRH analogues. This work showcased the ability of the dual divergent …

Artificial And Natural Nucleic Acid Self Assembling Systems, Marcus Wood

Wayne State University Dissertations

Nucleic acids are good candidates for nanomachine construction. They participate in all the processes of life, and so can function as structural building blocks and dynamic catalysts. However, to use nucleic acids as nanomachines, a better understanding of their material properties, how to design structures using them, and their dynamics is needed. We have tried to address these issues, in a small way, with nucleic acid force field development, an attempt at nanostructural design and synthesis using DNA, and a study of the RNA/protein regulatory dynamics of the tryptophan regulatory attenuation protein.

Development Of Chemical Inducers Of Dimerization For Screening Competitive Histone Deactelyase Inhibitors, Emily Lynn Aubie

Wayne State University Dissertations

Histone Deacetylase (HDAC) proteins are transcriptional regulators that affect histone proteins, which are involved in packaging of DNA into chromosomes. HDACs have been linked to the proliferation of cancer through their role in transcriptional regulation. Due to these findings, HDAC inhibitors have been explored as anti-cancer agents. Several HDAC inhibitors are currently in various stages of clinical trials, and the inhibitor suberoyl anilide hydroxamic acid (SAHA) has been FDA approved for treatment of cutaneous T-Cell lymphoma. Currently, most of the known HDAC inhibitors are non-selective, which causes non-specific binding to the active sites of all HDAC isoforms, including those not …

Synthesis And Characterization Of Metal Chalcogenide Nanostructured Materials For Thermoelectric Applications, Shreyashi Ganguly

Wayne State University Dissertations

The synthesis and characterization of metal chalcogenide nanostructured materials with the potential to exhibit enhanced thermoelectric (TE) properties is reported. The tellurides, specifically PbTe and Bi⊂2⊂Te⊂3⊂ (Bi⊂2⊂Te⊂3⊂–Sb⊂2⊂Te⊂3⊂ alloys) were selected as these are well established TE materials in bulk form. The approaches used for nanostructuring are (1) sol-gel assembly of discrete nanoparticles of PbTe, Bi⊂2⊂Te⊂3⊂, and Bi⊂2⊂Te⊂3⊂–⊂2⊂Te⊂3⊂ alloys, and (2) formation of heterostructured nanocomposites of PbTe nanoparticles in bulk Bi⊂2⊂Te⊂3⊂ (p– or n–doped) matrices.

Aerogels and xerogels of PbTe nanoparticles were synthesized by sol–gel assembly of discrete nanoparticles, leading to interconnected networks of nanoparticles and pores. The PbTe aerogel exhibited …

Exploring Potential Drug Target Sites In The Ribosome Using Cisplatin And Its Analogues, Keshab Rijal

Wayne State University Dissertations

Cis-diamminodichloridoplatinum (II), cisplatin, is an antitumor drug that has been used to treat several types of cancers. The reaction of cisplatin with DNA has been studied and discussed extensively in the literature; however, the effects of cisplatin on RNA function are poorly understood. In this thesis, two aspects of cisplatin, its preferred sites of interaction with RNA and its use as a chemical probe to gain accessibility information, were explored.

To understand the site-selectivity of cisplatin with RNA, model RNA constructs and full-length 16S rRNA were employed. The binding studies revealed a cisplatin preference for guanosine-rich sequences. Primer extensions in …

Synthesis Of N-Acetyl And C-Tert-Butyl Natural Amino Acid Substrates That Mimic Residues Of Polypeptides And Their Reactivity With [Feiv(O)(N4py)]2+: Kinetic And Mechanistic Investigations, Ashley Ann Campanali

Wayne State University Dissertations

This dissertation is divided into two chapters, the first chapter includes an introduction to reactive oxygen species and their reactions with proteins. The introduction also covers metal-based oxidants, including both heme and non-heme enzymes that activate dioxygen as well as complexes that mimic these enzymes. The work discussed in chapter one concerns the synthesis of amino acid substrates that mimic amino acid residues. Substrates synthesized were derived from Gln, Asn, Ile, Cys and Tyr. Once synthesized, these substrates were reacted with [FeIV(O)(N4Py)]2+ under pseudo-first order conditions. The mechanisms for the reactions of the most reactive substrates were investigated. Electron-transfer proton-transfer …

Isolation And Analysis Of Peptides Binding To Helix 69 Of E. Coli 23 S Rrna From M13 Phage Display, Moninderpal Kaur

Wayne State University Dissertations

Peptides binding to helix 69 of domain IV or residues 1906-1924, of 23 S rRNA of E.coli were being selected from a heptapeptide phage library. An experimental system including biotin labeling of RNA and then affinity selection through four rounds was being followed. After sequencing phage clones of the fourth round, two peptide sequences dominated the phage pool, STYTSVS and NQVANHQ. The later sequence was a unique sequence since this sequence contained an abundance of amino acid residues that are also present in the ribosome recycling factor, RRF, and known to make contacts with H69. Phage-display methodology demonstrated the rapid …

Applications Of Electronic Structure Theory To Problems In Unimolecular Dissociation And Inorganic And Biochemical Systems, Jia Zhou

Wayne State University Dissertations

In this dissertation, ab initio classical trajectory calculations have been carried out to study the dissociation of acetone radical cation, pentane-2,4-dione radical cation, and 1,3-cyclobutanedione radical cation. For acetone radical cation and pentane-2,4-dione radical cation, MP2 with bond additivity corrections generates a better potential energy surface at low cost and is thus used for molecular dynamics calculations. The dissociation of acetone radical cation is found to favor the loss of the newly formed methyl group in agreement with the experiments. The branching ratios of methyl loss were also calculated with different amount of excess energy and of specific mode excitation. …

New Insights Into The Mechanism Of Dna Replication On Unmodified And Benzo[A]Pyrene Modified Templates Using Surface Plasmon Resonance, Richard George Federley

Wayne State University Dissertations

DNA synthesis is critical to cell survival, and the enzyme DNA polymerase has had a great deal of time to evolve efficient strategies to perform synthesis. A variety of effects are induced by the identity of the incoming dNTP, and its ability to effectively base pair with the templating base. The presence of the next correct dNTP is known to induce a conformational change of the polymerase and lead to an increase in KF-DNA binding. Conversely, the presence of an incorrect dNTP is shown to lead to a destabilization and reduction in the levels of KF-DNA complexes formed. Using surface …

Laser-Assisted Single-Molecule Refolding, Rui Zhao

Wayne State University Dissertations

Non-coding RNAs must fold into precise secondary and tertiary structures in order to perform the biological functions. Due to the flexibility of RNA, the RNA folding energy landscape can be rugged and full of local minimum (kinetic trap). To provide a means to study kinetically trapped RNAs, we have developed a new technique combining single-molecule FRET detection with laser induced temperature jump. We have calibrated the magnitude of the temperature jump with 1˚C accuracy using gold micro-size sensor. The accuracy of temperature calibration was confirmed by close agreement between single-molecule and bulk DNA duplex melting experiments.

HIV 1 DIS RNAs …

Astrochemical Dynamics: Fundamental Studies Relevant To Titan's Atmosphere, Wilson Kamundia Gichuhi

Wayne State University Dissertations

This work presents results of primary fundamental photodissociation and state-specific ion-molecule dynamical studies that are relevant to understanding the formation and growth mechanisms of unsaturated hydrocarbon molecules, haze layers and aerosols in Titan's upper atmosphere. In the diacetylene dimer, it is shown, via laboratory studies combined with electronic structure calculations that the photodissociation of the dimer readily initiates atomic hydrogen (H) loss and atomic H transfer reactions forming two prototypes of resonantly stabilized free radicals, C8H3 and C4H3, respectively. In ethylamine cation, high-level ab initio calculations identify the complex dissociation pathways for the ground state CH3CH2NH2+ radical cation at 233.3 …

Thiomaleic Anhydride: A Linchpin For Organic Synthesis And Structural Verification Of A Nonprotein Antifreeze Oligosaccharide, Md Yeajur Rahaman Sardar

Wayne State University Dissertations

This dissertation consists of two parts of which the first develops the utility of α,β-unsaturated monothioanhydrides as a linchpins in multicomponent coupling reactions by processes involving addition to the double bond, cyclization onto the anhydride, and finally exploitation of the rich chemistry of the thioacid liberated in the cyclization. The second part of the thesis is concerned with verification of the structure of a nonprotein antifreeze oligosaccharide by the total synthesis of various authentic oligosaccharides and the comparison of spectroscopic data.

Chapter one starts with the introduction of the general characteristics and reactivity of thioacids, and their potential for application …

Synthesis, Redox Properties, And Langmuir Monolayer Formation Of Selected 3d- And 4d- Metalloamphiphiles, Sree Ramadevi Shanmugam

Wayne State University Dissertations

Transition metals containing amphiphilic compounds integrate various geometric, electronic, magnetic, and electrochemical properties together with the film forming properties. These compounds thereby find potential towards the fabrication of responsive films. This dissertation confers the synthesis and analysis of film forming properties of various redox-active metalloamphiphiles. Two new azido and thiocyanto bridged copper-based amphiphiles were synthesized and characterized by IR, UV-visible, and EPR spectroscopies, mass spectrometry, cyclic voltammetry, and elemental analysis. The redox studies show that both these complexes exhibit redox reversibility with only the azido bridged complex showing good redox cycling of about 50 times with minimal decomposition of less …

Nmr Solution Structures Of Two Hairpins Of E. Coli 16s Rrna: The Effects Of Mutations And Chemical Modifications On Structure And Function Of Rrna, Yu Liu

Wayne State University Dissertations

The structures of two functional mutants, the UC (G690U, U697C) and the QM mutants (G690A, G693C, A695C, U697A) of the 690 hairpin of E. coli 16S ribosomal RNA were determined by NMR. The UC mutant and the QM mutant with high biological function are able to fold into structures that are isomorphous with the wild-type 690 hairpin sequence. The structural comparisons among the functional mutants and the wild-type provides structural validation for previously identified specific functional groups that are crucial for maintaining function of the 690 hairpin. The key groups for maintaining the structure and function of the 690 loop …