Chemistry Commons^™

Influence Of Histidine Residues, Ph And Charge Interactions On Membrane-Spanning Peptides, Ashley N. Henderson

Graduate Theses and Dissertations

Designed transmembrane peptides were employed for investigations of histidine residues within the hydrophobic environment of the lipid bilayer by means of oriented solid-state deuterium NMR spectroscopy. Using the model peptide GWALP23 sequence (GGALW(LA)6LWLAGA) as a host framework, the effects of single and double histidine mutations were explored. Replacement of leucine residue 12 to polar neutral histidine had little influence on the peptide average orientation, however under strongly acidic pH conditions in DOPC bilayers, the histidine becomes positively charged (pKa 2.5) and the GWALP23-H12 peptide exits the membrane and adopts a surface-bound orientation. Conversely, mutation of leucine 14 to neutral histidine …

Bioorthogonal Reactions: Synthesis And Evaluation Of Different Ligands In Copper Catalyzed Azide-Alkyne1,3-Dipolar Cycloaddition (Cuaac), Zainab Abdullah Almansaf

Graduate Theses and Dissertations

The Copper CatalyzedAzide-Alkyne1,3-Dipolar Cycloaddition (CuAAC) reaction has unique features that qualify it to be one of the best click reactions. Its applications have been shown in different aspects and for multiple purposes. The oxidative degradation of biological systems (labile proteins and live cells) is, however, generally recognized as the major problem when using this reaction in living systems. Reactive oxidation species can be easily produced in the presence of copper(II), ascorbate and air, and this is the main cause of toxicity. However, the uses of ligands have shown a major impact on reducing copper toxicity, protecting Cu(I) from the redox …

Investigation Of The Interaction Of Dimeric Ruthenium Complexes With Cytochrome B5, Christopher Dain Rupar

Graduate Theses and Dissertations

Photoreactive complexes to study the kinetics of electron transfer of proteins have been in use for a long time. It has always been speculated that complexes bind near the heme or the electron transfer reaction would not occur. But it is unkown exactly how the complex interacts with the protein. The structural, thermodynamic, and kinetic properties of rat liver microsomal cytochrome b5 were investigated when bound to ruthenium dimer complexes. Heteronuclear Single Quantum Coherence studies support a dynamic binding model of a dimer Ru complex bound near the protein’s heme involving residues H39, E44, G42, V61, G62, and H63. The …

Mechanism Of Rapid Electron Transfer Reactions Involving Cytochrome Bc1, Cytochrome C And Cytochrome Oxidase, Jeremy Erik Durchman

Graduate Theses and Dissertations

Electron transfer between mitochondrial proteins complexes represents the primary means by which living things acquire the requisite energy for survival. The coupling of electron transfer to proton translocation creates an electrochemical gradient that drives the synthesis of highly energetic compounds such as ATP. The purpose of these studies is to measure rates of electron transfer and elucidate the important governing factors in the redox events involving cytochrome bc1, cytochrome c and cytochrome oxidase. Using rapid initiation of redox events triggered by laser flash excitation of ruthenium compounds, and strategically monitoring unique spectral properties of these proteins in the visible region …

Designing Fret Assays To Study Electrostatic Interactions Pertaining To The Binding Of Intrinsically Disordered Proteins, Ashley Ann Howard

Graduate Theses and Dissertations

Fibroblast growth factor receptor plays a major role in several biological processes. Without FGFR, a human cannot live. FGFR is involved in cell differentiation and wound healing. Of course, if FGFR signaling becomes unregulated, it causes severe distress in the body. Several cancers are contributed to high signaling levels, as well as developmental conditions like rickets and Kallmann’s syndrome. FGFR is thought to undergo an auto-inhibition (or self-regulatory) process in order to try to facilitate regulation. The exact method of this inhibition is currently unknown, but is proposed to involve the unstructured acid box region of FGFR. We developed a …

The Effects Of Molecular Chaperones On Tau Fibril Assembly, Ahmed Omran

Electronic Theses and Dissertations

The accumulation of microtubule-associated protein tau into fibrillar aggregates is the hallmark of Alzheimer’s disease and other neurodegenerative disorders, collectively referred to as tauopathies. Fibrils can propagate from one cell to the next and spread throughout the brain. However, a study shows that only small aggregates can be taken up by cultured neuronal cells. The mechanisms that lead to the breakage of fibrils into smaller fragments remain unknown. In yeast, the AAA+ chaperone HSP104 processes the reactivation of protein aggregates and is responsible for fragmentation of fibrils. This study focused on investigating the effects of molecular chaperones on tau fibrils …

New Strategies To Reveal Protein Candidates In Protein-Protein Interactome Study, Meng-Chieh Chen

Open Access Theses

Comprehensive protein-protein interaction network analysis can help reveal protein functions in a system-wide manner. A reliable knowledgebase of interaction networks is not only important for selecting the candidates for drug therapies, but also for evaluating the disease risk. In current interaction databases, 322579 interactions comprised of 56460 proteins have been reported (statistical analysis from APID: Agile Protein Interaction DataAnalyzer; http://bioinfow.dep.usal.es/apid/index.htm). The huge datasets are contributed mainly by yeast -two -hybrid (Y2H) screening and affinity-purification followed by mass spectrometry (AP-MS). High false positive rates and failing to cover certain interaction categories are the limitations of these two methods. Here, we developed …

Resonant Two-Photon Ionization Studies Of Non Covalent Interactions In Halo Aromatic Clusters And Spin-Orbit Coupling Modeling In Mono-Halocarbenes, Silver Nyambo

Dissertations (1934 -)

Non-covalent interactions in halobenzenes (PhX) (X=F, Cl, Br) and phenylamine (C₆ H₅ NH₂ ) have been studied here using resonance two-photon ionization (R2PI) spectroscopy combined with a linear TOF-mass spectrometer. Their interaction with polar molecules in form of ammonia (NH ₃ ) and trifluorohalomethanes (CF₃ X) has also been studied. DFT and TD-DFT calculations using M06-2X functionals were carried out on different cluster conformations to compliment experimental results. A general trend of broadness in homogenous dimers (PhX)₂ , has been attributed to mainly the presence of multiple cluster isomers and Frank-Condon activity in the low …

Monodentate, Bidentate And Photocrosslinkable Thiol Ligands For Improving Aqueous Biocompatible Quantum Dots, Hiroko Takeuchi

Graduate Theses and Dissertations

Water-soluble Quantum Dots (QDs) are highly sensitive fluorescent probes that are often used to study biological species. One of the most common ways to render QDs water-soluble for such applications is to apply hydrophilic thiolated ligands to the QD surface. However, these ligands are labile and can be easily exchanged on the QD surface, which can severely limit their application. As one way to overcome this limitation while maintaining a small colloidal size of QDs, we developed a method to stabilize hydrophilic thiolated ligands on the surface of QDs through the formation of a crosslinked shell using a photocrosslinking approach. …

Design, Synthesis, And Evaluation Of Molecular Inhibitors For Biologically Relevant Enzymes, Sarah Emma St. John

Open Access Dissertations

The work in this thesis details the design, synthesis, and biological evaluation of molecular inhibitors for the inhibition of biologically relevant enzymes. The first three chapters of this thesis concern the polyphenol resveratrol and its inhibition of the quinone reductase 2 (QR2) enzyme. The work on this subject resulted in the complete design, synthesis, biological and structural evaluation of a second generation library of resveratrol analogues. From this work we identified a novel resveratrol analogue that inhibits QR2 in a previously unknown binding orientation. The fourth chapter of this thesis details the de novo design of molecules for the inhibition …

Gas-Phase Covalent And Non-Covalent Ion/Ion Chemistry Of Biological Macromolecules, John Robert Stutzman

Open Access Dissertations

Gas-phase ion/ion chemistry involves the interaction of oppositely charged ions inside of the mass spectrometer. During this gas-phase chemistry, particle transfer (i.e., proton and electron) or synthesis can occur at rapid reaction rates. Particle transfer represents a mature area of ion/ion chemistry, while selective covalent modification represents a fairly new area of gas-phase chemistry. Gas-phase covalent chemistry is based on traditional solution phase organic chemistry.

The work demonstrated in this dissertation greatly involves gas-phase covalent and non-covalent Schiff base chemistry on peptide and protein ions. The reagent dianion, 4-formyl 1,3-benzene disulfonic acid, has been used to covalently modify unprotonated primary …

Part I - A Study Of The Formation Of Carbenes By Elimination Of Α-Bromosilanes And Application Toward The Synthesis Of Transition Metal Complexed Quinone Methide Analogs. Part Ii - Development Of Novel 7-Membered Ring Carbene Ligands For Palladium Catalyzed Cross Coupling Reactions., Christian Michael Loeschel

Graduate Theses and Dissertations

In part I, we wish to report our approaches toward transition metal complexed ortho-quinone methide analogs. ortho-Quinone Methides are a class of highly reactive compounds with a wide range of chemical and biological applications. Previously, a stable iron complexed benzannulated 5-membered ring quinone methide analog was reported by Allison and Neal27. Herein, we report our approaches to improve the reactivity of that system by removing benzannulation as well as changing the metal from iron to manganese and rhenium.

Furthermore, a methodological study on generating carbenes under mild conditions by elimination of α-halosilanes and its application towards metal complexed quinone methide …

Development Of An Assay To Screen For Novel Proteins From Bacillus Thuringiensis With Antibacterial Activity, Auriole T. Tamegnon

Theses and Dissertations - UTB/UTPA

Bacillus thuringiensis (Bt) produces the non specific Cyt protein and the specific Cry protein. Past research has shown these proteins are toxic to insects, red blood cells, cancer cells, and some bacteria. While many antibacterial substances are known to exist, efforts to find new ones still continue. In this project we used Bt 6-2-56 (containing a novel filament associated parasporal body which appears non-toxic to insects and protozoan) and Bt 4Q13 (which has been shown to have activity against E. coli and S. aureus) to develop a simple, easy, scalable assay in a 96 well Microtitre plate to look for …

Visualizing The Spatial Localization Of Active Matrix Metalloproteinases (Mmps) Using Maldi Imaging Ms, Sasirekha Muruganantham

Graduate Theses and Dissertations

Biomaterial implantation induces the foreign body response (FBR). Development of longer-term implants relies on the thorough understanding of the FBR. The progression of the FBR is regulated by a number of biomolecules including cytokines, chemokines, and matrix metalloproteinases (MMPs). The nature of the FBR requires the spatial and temporal regulation of these mediators. MMPs are an extremely large and diverse group of enzymes that play key roles in regulating the FBR. Precise spatiotemporal regulation of MMPs defines their proteolytic activities. The aim of this project is to develop a new bioanalytical method to visualize the localization of active MMPs at …

The Biophysical Analysis Of The Human Telomeric Repeat (Ttaggg)4 And Characterization Of Porphyrin Binding In Potassium Solutions, Cosimo Antonacci

Seton Hall University Dissertations and Theses (ETDs)

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Structural And Thermodynamic Parameters Associated With The Interaction Of Cobalt (Iii) Complexes And Duplex Dna, Jaime M. Ferreira

Seton Hall University Dissertations and Theses (ETDs)

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Microcapsule Biosensors Based On Competitive Binding And Fluorescence Resonance Energy Transfer Assays, Swetha Chinnayelka

Doctoral Dissertations

Fluorescent sensing systems offer the potential for minimally invasive monitoring with implantable devices, but they require carrier technologies that provide suitable immobilization, accessibility, and biocompatibility while maintaining adequate response characteristics. Towards the development of this goal, a general design of a biosensor with the capability of detecting different metabolites was investigated. The approach is based on the encapsulation of a competitive binding assay in microcapsules and monitoring the changes in fluorescence resonance energy transfer (FRET) in the presence of analyte. To experimentally demonstrate this type of sensing system, glucose was chosen as the model target analyte. The design, fabrication, and …

Synthesis Of Novel Porphyrazines And Binding Studies To Dna Quadruplexes, Carlos Ramirez

Seton Hall University Dissertations and Theses (ETDs)

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A Characterization Of Extractable, Hydroxylated Fatty Acid Bearing Components In Legionella Pneumophila, Jonathan R. Lane

Electronic Theses and Dissertations

Extraction of the lipids of Legionella pneumophila yields phases unlike those produced from other Gram-negative bacteria. A viscous interface forms between the aqueous (wash) and organic phases. More than half of the hydroxylated fatty acids were found distributed between the aqueous phase and the interfacial material, fractions in which such constituents have not been reported in other Gram-negative species. It was further observed that after the material from the aqueous/interfacial phase was dissolved in methanol or chloroform/methanol (2:1 (V/V)), the addition of acetone would create a white, flocculent precipitate. Analyses showed that the supernatant contained fatty acids that were nonhydroxylated …