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Using Resonance Raman Cross-Section Data To Estimate The Spin State Populations Of Cytochromes P450, Piotr J. Mak, Qianhong Zhu, James R. Kincaid

Chemistry Faculty Research and Publications

The cytochromes P450 (CYPs) are heme proteins responsible for the oxidation of xenobiotics and pharmaceuticals and the biosynthesis of essential steroid products. In all cases, substrate binding initiates the enzymatic cycle, converting ferric low-spin to high-spin state, with the efficiency of the conversion varying widely for different substrates, so documentation of this conversion for a given substrate is an important objective. Resonance Raman (rR) spectroscopy can effectively yield distinctive frequencies for the ν₃ ‘spin state marker’ bands. Here, employing a reference cytochrome P450 (CYP101), the intensities of the ν₃ modes (I_LS) and (I_{HS …}

Obstacles And Solutions To Studying Functional Adhesives Using Vibrational Sum-Frequency Generation Spectroscopy, Angela Renee Andersen

Theses and Dissertations

Important aspects of adhesion occur at interfaces, including structures that may be different from those in the bulk materials. However, probing the orientation of molecules in functional adhesives poses a significant challenge because adhesive molecules are always located at a buried interface. The limited penetration depth of surface-specific analysis prohibits the study of buried interfaces using those techniques. The large quantity of bulk molecules relative to the adhesive molecules interacting at the interface results in the bulk signal swamping out adhesive signal in bulk analysis techniques. An interface-specific technique is required to study functional adhesives. One such technique that has …

An Insight Into Asymmetric Synthesis And Bioorganic Applications Of Novel Cα- Methyl-Lysine, - Proline, - Nipocotic Acid Analogues, Souvik Banerjee

Dissertations

Prochiral malonic diesters consisting of a quaternary carbon center have been successfully converted into a different set of tBoc-Fmoc-α2,2-methyllysine-OH analogues through chiral malonic half-ester intermediates achieved via enzymatic (Pig Liver Esterase, PLE) hydrolysis. The selection of chiral half-ester intermediates, which vary from 1 to 6 methylene units in the side chain, are achieved in high optical purity (92% - 97% ee) and in good yields (65% - 72%). The PLE hydrolysis of malonic diesters with a variety of side chain lengths observed to obey the Jones’s PLE model as evidenced from the stereochemical configurations of the resulting chiral half-esters. The …

Gfsa Encodes A Novel Galactofuranosyltransferase Involved In Biosynthesis Of Galactofuranose Antigen Of O-Glycan In Aspergillus Nidulans And Aspergillus Fumigatus, Yuji Komachi, Shintaro Hatakeyama, Haruka Motomatsu, Taiki Futagami, Karina Kizjakina, Pablo Sobrado, Keisuke Ekino, Kaoru Takegawa, Masatoshi Goto, Yoshiyuki Nomura, Takuji Oka

Chemistry Faculty Research & Creative Works

Summary: The cells wall of filamentous fungi in the genus Aspergillus has galactofuranose (Galf)-containing polysaccharides and glycoconjugates, including O-glycans, N-glycans, fungal-type galactomannan and glycosylinositolphosphoceramide, which are important for cell wall integrity. Here, we attempted to identify galactofuranosyltransferases that couple Galf monomers onto other wall components in Aspergillus nidulans. Using reverse-genetic and biochemical approaches, we identified that the AN8677 gene encoded a galactofuranosyltransferase, which we called GfsA, involved in Galf antigen biosynthesis. Disruption of gfsA reduced binding of β-Galf-specific antibody EB-A2 to O-glycosylated WscA protein and galactomannoproteins. The results of an in-vitroGalf antigen synthase assay revealed that GfsA has β1,5- or …

Electrospinning Polymer Blends For Biomimetic Scaffolds For Acl Tissue Engineering, Vanessa Lizeth Garcia

Theses and Dissertations - UTB/UTPA

The anterior cruciate ligament (ACL) rupture is one of the most common knee injuries. Current ACL reconstructive strategies consist of using an autograft or an allograft to replace the ligament. However, limitations have led researchers to investigate tissue engineered grafts, known as scaffolds, through electrospinning. Scaffolds made of natural and synthetic polymer blends have the potential to promote cell adhesion while having strong mechanical properties. However, enzymes found in the knee are known to degrade tissues and affect the healing of intra-articular injuries. Results suggest that the natural polymers used in this study modify the thermal properties and tensile strength …

Remediation Of Copper(Ii) And Lead(Ii) From Aqueous Solution Using Engineered Iron Oxide And Manganese Oxide Nanomaterials, Carlos Tamez Jr.

Theses and Dissertations - UTB/UTPA

Nano-sized Fe3O4, Fe2O3, Mn3O4, and MnO2 were synthesized by titration/precipitation and characterized using powder XRD. pH assays determined that optimum binding occurred at pH 4 for Fe3O4 and Fe2O3 and pH 3 for Mn3O4 and MnO2. Maximum adsorption of Cu(II) and Pb(II) occurred within 20 min or less of contact with the nanomaterials. The synthesized nanomaterials showed a binding preference for Pb(II) over Cu(II) at concentrations above 50 ppm. Batch studies also showed no significant reduction in the binding of copper and lead to either Fe3O4, Fe2O3, Mn3O4, or MnO2 in the presence of Na+ , K+ , Mg2+ or …

Investigation Into The Effects Of Pegylation On The Thermodynamic Stability Of The Ww Domain, Sam S. Matthews

Theses and Dissertations

The covalent attachment of poly(ethylene glycol) (PEG) to a protein surface (known as PEGylation), has been demonstrated to increase the serum half-life of therapeutic proteins by reducing kidney clearance and immunogenicity and by protecting against proteolysis. Theses beneficial effects could be further enhanced if PEGylation consistently increased protein conformational stability (i.e. the difference in free energy between the folded and unfolded states). However, the effects of PEGylation on protein conformational stability are unpredictable; PEGylation has been reported to increase, decrease, or have no effect on the conformational stability of medicinal proteins.This thesis details the results of two studies aimed at …

Synthesis Of Resveratrol Ester Derivatives, Daniel Ressler

Electronic Theses and Dissertations

The goal of this research project was to synthesize derivatives of transresveratrol. In order for resveratrol to be activated and used by the body it needs to bind to Human Serum Albumin (HSA), a protein in blood plasma. The derivatives were synthesized to improve the ability of resveratrol to enter cells as well as improve their ability to bind to HSA. The three derivatives that were synthesized have converted one of the hydroxyl groups on resveratrol to an ether with a methylene chain terminated by a carboxylic acid. By varying the lengths of the methylene chain we varied the water …

Synthesis And Characterization Of A New Cyano-Substituted Tris(Pyrazolyl)Borate And Its Thallium(I) Complex, Bozumeh Som

Electronic Theses and Dissertations

A new cyanoscorpionate - tris(4-cyano-3,5-diphenylpyrazolyl)borate (Tp^Ph2,4CN) has been synthesized and characterized. The thallium complex of this ligand TlTp^Ph2,4CN has also been prepared and characterized by FT-IR, ¹H NMR, and single-crystal X-ray-diffraction. The complex TlTp^Ph2,4CN crystalized in the monoclinic space group C2/c with unit cell a = 14.6697(10) Å, b = 13.9493(10) Å, c = 19.3347(12) Å, and b= 91.761(2)°. Structural comparison of TlTp^Ph2,4CN with analogous complexes demonstrated the effects of both steric and electron-withdrawing substituents on coordination geometry and the electronic properties of the metal ion. There were short contacts between the cyano groups …

Synthesis Of Ferrocene Copolymers And Investigation Of Their Electrochemical Properties., Alzharani Ahmed

Electronic Theses & Dissertations

Ferrocene is an organometallic compound. It is a classical metallocene consisting of two cyclopentadienyl rings bound on opposite sides of a central iron atom. Such organometallic compounds are also called sandwich compounds. Ferrocene copolymers have well known electrochemical capabilities. The main objective of this thesis is to synthesize vinyl ferrocene copolymers and test their electrochemical properties in aqueous solutions with different electrolytes (sodium nitrate, sodium perchlorate, and phosphate buffered saline). Vinylferrocene and 3-phenyl[5]ferrocenophane-1,5- dimethylene were synthesized using a Wittig reaction. Both ferrocene monomers were copolymerized with N-ethylmaleimide and N-phenylmaleimide and the resulting polymers were analyzed by Gel Permeation chromatography, IR …

Identification Of Disufide Bond Formation Between Mitoneet And Glutamate Dehydrogenase 1., Morgan Roberts, Jacquelyn Crail, Megan Laffoon, William Fernandez, Michael Menze, Mary Konkle

Faculty and Staff Scholarship

MitoNEET is a protein that was identified as a drug target for diabetes, but its cellular function as well as its role in diabetes remains elusive. Protein pull-down experiments identified glutamate dehydrogenase 1 (GDH1) as a potential binding partner. GDH1 is a key metabolic enzyme with emerging roles in insulin regulation. MitoNEET forms a covalent complex with GDH1 through disulfide bond formation and acts as an activator. Proteomic analysis identified the specific cysteine residues that participate in the disulfide bond. This is the first report that effectively links mitoNEET to activation of the insulin regulator GDH1.

Lipid Production By Microalgae Treating Municipal Wastewater, James Edward Kelley

Master's Theses

Microalgae hold much promise as a feedstock in liquid biofuel production. Lipid content of microalgae cells range from 30-80% dry weight of biomass. It is projected that microalgae can produce between 1,000-6,500 gallons/acre/year of oil. Currently, production of industrial algae operates in open raceway ponds that use minimal capital and energy inputs to culture algae. Raceway ponds can also be used to grow microalgae from municipal waste streams. Although high biomass productivity can be achieved in these systems, there remains a large production gap between large volumes of biomass cultivation and high lipid content from microalgae cells. Low lipid content …

The Influence Of Hydrogeomorphology, Soil Redox Conditions, And Salinity On The Spatial Zoning Of Saltgrass, Salt Rush, And Cattails In Scotts Creek Marsh, Swanton Pacific Ranch, Ca, Mark D. Gormley

Master's Theses

Scotts Creek Marsh (SCM) is a small coastal wetland ecosystem in Davenport, CA. The vegetation of SCM is dominated by three halophytic zones comprised of saltgrass, salt rush, cattails. The objectives of the study were (i) to investigate the variables that influence the zoning of the three dominant halophyte communities in SCM and (ii) to the test the effectiveness of Indicator of Reduction in Soil (IRIS) tubes to indicate the reduction of S. The study examined the following parameters from April 6 to July 21, 2013: (i) the HGM of Scotts Creek Marsh, (ii) soil oxidation and reduction (redox) conditions, …

Developing A Presumptive Test For Select Synthetic Cannabinoids, Carrie Snyder

Graduate Theses and Dissertations

Synthetic cannabinoids (SC's) began to gain popularity around the world in 2009. Since then, many of the compounds have been outlawed and methods developed to detect them and their metabolites using mass spectrometry. Our work investigated the possibility of developing a colorimetric presumptive test. The SC JWH-019 was synthesized and its ketone targeted as a possible reaction site. Many SC's contain ketones and thus a reaction at this site would be applicable to many of the compounds. Since JWH-019 is costly and time consuming to synthesize, much of the experimental work was done using benzophenone (BP). BP contains a diaryl …

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. …

The Spectral Properties Of (-)-Epigallocatechin 3-O-Gallate (Egcg) Fluorescence In Different Solvents: Dependence On Solvent Polarity, Vladislav Snitsarev, Michael N. Young, Ross M.S. Miller, David P. Rotella

Department of Chemistry and Biochemistry Faculty Scholarship and Creative Works

(-)-Epigallocatechin 3-O-gallate (EGCG) a molecule found in green tea and known for a plethora of bioactive properties is an inhibitor of heat shock protein 90 (HSP90), a protein of interest as a target for cancer and neuroprotection. Determination of the spectral properties of EGCG fluorescence in environments similar to those of binding sites found in proteins provides an important tool to directly study protein-EGCG interactions. The goal of this study is to examine the spectral properties of EGCG fluorescence in an aqueous buffer (AB) at pH=7.0, acetonitrile (AN) (a polar aprotic solvent), dimethylsulfoxide (DMSO) (a polar aprotic solvent), and ethanol …

Acoustic Droplet Vaporization In Biology And Medicine, Chung-Yin Lin, William G. Pitt

Faculty Publications

This paper reviews the literature regarding the use of acoustic droplet vaporization (ADV) in clinical applications of imaging, embolic therapy, and therapeutic delivery. ADV is a physical process in which the pressure waves of ultrasound induce a phase transition that causes superheated liquid nanodroplets to form gas bubbles. The bubbles provide ultrasonic imaging contrast and other functions. ADV of perfluoropentane was used extensively in imaging for preclinical trials in the 1990s, but its use declined rapidly with the advent of other imaging agents. In the last decade, ADV was proposed and explored for embolic occlusion therapy, drug delivery, aberration correction, …

Investigation Of The Structure And Dynamics Of Regioisomeric Eu³⁺ And Gd³⁺ Chelates Of Nb-Dotma: Implications For Mri Contrast Agent Design, Benjamin Charles Webber

Dissertations and Theses

The detection of disease and abnormal pathology by magnetic resonance imaging (MRI) has been aided significantly by the use of gadolinium (Gd³⁺)-based contrast agents (CAs) over the past three decades. MRI and MRI CAs play a critical role in diagnosing tumors and diseases of the central nervous system. The agents used clinically have been shown to safely increase MRI contrast despite the toxicity of Gd³⁺, owing to the high kinetic and thermodynamic stability of these chelates. However, current CAs enhance contrast at a small fraction of what is theoretically possible. This leads to the necessity of …

Examination Of Tyrosine/Adenine Stacking Interactions In Protein Complexes, Kari L. Copeland, Samuel J. Pellock, James R. Cox, Mauricio L. Cafiero, Gregory S. Tschumper

Chemistry Faculty Research & Creative Works

The π-stacking interactions between tyrosine amino acid side chains and adenine-bearing ligands are examined. Crystalline protein structures from the protein data bank (PDB) exhibiting face-to-face tyrosine/adenine arrangements were used to construct 20 unique 4-methylphenol/N9-methyladenine (p-cresol/9MeA) model systems. Full geometry optimization of the 20 crystal structures with the M06-2X density functional theory method identified 11 unique low-energy conformations. CCSD(T) complete basis set (CBS) limit interaction energies were estimated for all of the structures to determine the magnitude of the interaction between the two ring systems. CCSD(T) computations with double-ζ basis sets (e.g., 6-31G*(0.25) and aug-cc-pVDZ) indicate that the MP2 method overbinds …

Troika Of Single Particle Tracking Programing: Snr Enhancement, Particle Identification, And Mapping, Lydia Kisley

Faculty Scholarship

Single particle tracking (SPT) techniques provide a microscopic approach to probe in vivo and in vitro structure and reactions. Automatic analysis of SPT data with high efficiency and accuracy spurs the development of SPT algorithms. In this perspective, we review a range of available techniques used in SPT analysis programs. In addition, we present an example SPT program step-by-step to provide a guide so that researchers can use, modify, and/or write a SPT program for their own purposes. © 2014 the Owner Societies.

Role Of Ser-257 In The Sliding Mechanism Of Nadp(H) In The Reaction Catalyzed By The Aspergillus Fumigatus Flavin-Dependent Ornithine N ⁵-Monooxygenase Sida, Carolyn Shirey, Somayesadat Badieyan, Pablo Sobrado

Chemistry Faculty Research & Creative Works

SidA (siderophore A) is a flavin-dependent N-hydroxylating monooxygenase that is essential for virulence in Aspergillus fumigatus. SidA catalyzes the NADPH- and oxygen-dependent formation of N5-hydroxyornithine. In this reaction, NADPH reduces the flavin, and the resulting NADP+ is the last product to be released. The presence of NADP+ is essential for activity, as it is required for stabilization of the C4a-hydroperoxyflavin, which is the hydroxylating species. As part of our efforts to determine the molecular details of the role of NADP(H) in catalysis, we targeted Ser-257 for site-directed mutagenesis and performed extensive characterization of the S257A enzyme. Using a combination of …

Two Homologous Ef-G Proteins From Pseudomonas Aeruginosa Exhibit Distinct Functions, Stephanie O. Palmer, Edna Y. Rangel, Yanmei Hu, Alexis T. Tran, James M. Bullard

School of Integrative Biological & Chemical Sciences (Formerly Dept. of Chemistry)

Genes encoding two proteins corresponding to elongation factor G (EF-G) were cloned from Pseudomonas aeruginosa. The proteins encoded by these genes are both members of the EFG I subfamily. The gene encoding one of the forms of EF-G is located in the str operon and the resulting protein is referred to as EF-G1A while the gene encoding the other form of EF-G is located in another part of the genome and the resulting protein is referred to as EF-G1B. These proteins were expressed and purified to 98% homogeneity. Sequence analysis indicated the two proteins are 90/84% similar/identical. In other …

Thiol-Containing Compounds For The Removal Of Elements From Tissues And Formulations Therefor, Boyd E. Haley, David A. Atwood, Niladri Gupta

Chemistry Faculty Patents

Methods and pharmaceutical formulations for ameliorating heavy metal toxicity and/or oxidative stress are disclosed, comprising administering pharmaceutically effective amounts of ligands according to the present disclosure.

To see the remainder of the abstract, please download this patent.

Development Of A Biosensor For Investigating Membrane Curvature Sorting, Joshua C. Black

Electronic Theses and Dissertations

The physical structure of cellular membranes plays a critical role in lipid and protein sorting. A novel biosensor was developed to probe the influence of curvature on sorting. This biosensor mimics large, two-dimensional membranes in dynamic equilibrium, achieves high spatial resolution between curvature and molecules of interest, and has high sensitivity, enough for single particle detection. The biosensor consists of continuous supported lipid bilayer formed over nanoparticles (40 to 200 nm diameter) deposited on a glass substrate. The nanoparticles determine the extent of curvature. This biosensor is the first to observe large-scale 2-dimensional diffusion of biomolecules on a supported lipid …

Probing Vibrationally Mediated Ultrafast Excited-State Reaction Dynamics With Multireference (Caspt2) Trajectories, Patrick Z. El-Khoury, Saju Joseph, Igor Schapiro, Samer Gozem, Massimo Olivucci, Alexander N. Tarnovsky

Chemistry Faculty Publications

Excited-state trajectories computed at the complete active space second-order perturbation theory (CASPT2) reveal how vibrational excitation controls the molecular approach to the intersection space that drives the photodissociation of a prototypical halogenated methyl radical, namely CF2I. Translating the Franck-Condon structure along the ground-state CASPT2 vibrational modes in this system followed by propagating the displaced structures in the first excited doublet state simulates specific vibrational excitations and vibrationally mediated dynamics, respectively. Three distinct situations are encountered: the trajectories (i) converge to an energetically flat segment of the intersection space, (ii) locate a segment of the intersection space, and (iii) access a …

Substrate-Dependent Dynamics Of Udp-Galactopyranose Mutase: Implications For Drug Design, Leonardo Boechi, Cesar Augusto F. De Oliveira, Isabel Da Fonseca, Karina Kizjakina, Pablo Sobrado, John J. Tanner, J. Andrew Mccammon

Chemistry Faculty Research & Creative Works

Trypanosoma cruzi is the causative agent of Chagas disease, a neglected tropical disease that represents one of the major health challenges of the Latin American countries. Successful efforts were made during the last few decades to control the transmission of this disease, but there is still no treatment for the 10 million adults in the chronic phase of the disease. In T. cruzi, as well as in other pathogens, the flavoenzyme UDP-galactopyranose mutase (UGM) catalyzes the conversion of UDP-galactopyranose to UDP-galactofuranose, a precursor of the cell surface b-galactofuranose that is involved in the virulence of the pathogen. The fact that …

Cytochrome P450 Family 1 Inhibitors And Structure-Activity Relationships, Jiawang Liu, Jayalakshmi Sridhar, Maryam Foroozesh

Faculty and Staff Publications

With the widespread use of O-alkoxyresorufin dealkylation assays since the 1990s, thousands of inhibitors of cytochrome P450 family 1 enzymes (P450s 1A1, 1A2, and 1B1) have been identified and studied. Generally, planar polycyclic molecules such as polycyclic aromatic hydrocarbons, stilbenoids, and flavonoids are considered to potentially be effective inhibitors of these enzymes, however, the details of the structure-activity relationships and selectivity of these inhibitors are still ambiguous. In this review, we thoroughly discuss the selectivity of many representative P450 family 1 inhibitors reported in the past 20 years through a meta-analysis.

Microbial Natural Products: Molecular Blueprints For Antitumor Drugs, Lesley Ann Giddings, David J. Newman

Chemistry: Faculty Publications

Microbes from two of the three domains of life, the Prokarya, and Eukarya, continue to serve as rich sources of structurally complex chemical scaffolds that have proven to be essential for the development of anticancer therapeutics. This review describes only a handful of exemplary natural products and their derivatives as well as those that have served as elegant blueprints for the development of novel synthetic structures that are either currently in use or in clinical or preclinical trials together with some of their earlier analogs in some cases whose failure to proceed aided in the derivation of later compounds. In …

Mri Characterization Of Radiation Necrosis In An Animal Model: Time To Onset, Progression, And Therapeutic Response, Xiaoyu Jiang

All Theses and Dissertations (ETDs)

Radiation necrosis is a severe, but late occurring type of injury to normal tissue, within and surrounding a radiation treatment field, which can lead to significant complications for neurooncology patients. Radiation necrosis is difficult to distinguish from recurrent tumor by either neurologic examination or clinical imaging protocols. Concerns for the development of radiation necrosis often limit therapeutic radiation doses. Current treatment options for radiation necrosis are limited. The development of solutions to these clinical challenges has been hampered by an appropriate animal model of radiation necrosis.

With a novel mouse model of radiation necrosis developed in our lab employing a …

Laser Vaporization Methods For The Synthesis Of Metal And Semiconductor Nanoparticles; Graphene, Doped Graphene And Nanoparticles Supported On Graphene, Parichehr Afshani

Theses and Dissertations

The major objective of the research described in this dissertation is the development of new laser vaporization methods for the synthesis of metal and semiconductor nanoparticles, graphene, B- and N-doped graphene, and metal and semiconductor nanoparticles supported on graphene. These methods include the Laser Vaporization Controlled Condensation (LVCC) approach, which has been used in this work for the synthesis of: (1) gold nanoparticles supported on ceria and zirconia nanoparticles for the low temperature oxidation of carbon monoxide, and (2) graphene, boron- and nitrogen-doped graphene, hydrogen-terminated graphene (HTG), metal nanoparticles supported on graphene, and graphene quantum dots. The gold nanoparticles supported …