Physical Sciences and Mathematics Commons^™

Development Of Fluorescence Based Approaches To Understand Astrocyte Biology In The Context Of Nicotine And Nicotinic Receptor Activity, Surya P. Aryal

Theses and Dissertations--Chemistry

Smoking and tobacco use (STU) is a major global health problem and worldwide more than six million people die due to tobacco related diseases each year. Although majority of smokers try to quit smoking several times in their life, traditional therapeutic approaches, which focus only on neuronal cells, have a very low success rate. Understanding the effect of nicotine on glial cells, synaptic communication and blood vasculature in the brain can provide further insights on the neurobiology of substance abuse and can potentially help to design better therapeutic approaches. Glial cells are non-excitable cells in the brain which do not …

Chemical Shift Assignments Of The N-Terminal Domain Of Psd95 (Psd95-Nt), Yonghong Zhang, Johannes W. Hell, James B. Ames

Chemistry Faculty Publications and Presentations

Postsynaptic density protein-95 (PSD95) contributes to the postsynaptic architecture of neuronal synapses and plays an important role in controlling synaptic plasticity. The N-terminal domain of PSD95 (residues 1–71, called PSD95-NT) interacts with target proteins (calmodulin, α-actinin-1 and CDKL5), which regulate the Ca2+-dependent degradation of glutamate receptors. We report complete backbone NMR chemical shift assignments of PSD95-NT (BMRB No. 50752).

Sulfonamide Synthesis Via Calcium Triflimide Activation Of Sulfonyl Fluorides, Nicholas Ball, Paramita Mukherjee, Cristian P. Woroch, Leah Cleary, Mark Rusznak, Ryan W. Franzese, Matthew R. Reese, Joseph W. Tucker, John M. Humphrey, Sarah M. Etuk, Sabrina C. Kwan, Christopher W. Am Ende

Pomona Faculty Publications and Research

A method using calcium triflimide [Ca(NTf₂)₂] as a Lewis acid to activate sulfonyl fluorides toward nucleophilic addition with amines is described. The reaction converts a wide array of sterically and electronically diverse sulfonyl fluorides and amines into the corresponding sulfonamides in good yield.

Calcium-Mediated Control Of S100 Proteins: Allosteric Communication Via An Agitator/Signal Blocking Mechanism., Yiming Xiao, Gary S Shaw, Lars Konermann

Chemistry Publications

Allosteric proteins possess dynamically coupled residues for the propagation of input signals to distant target binding sites. The input signals usually correspond to "effector is present" or "effector is not present". Many aspects of allosteric regulation remain incompletely understood. This work focused on S100A11, a dimeric EF-hand protein with two hydrophobic target binding sites. An annexin peptide (Ax) served as the target. Target binding is allosterically controlled by Ca²⁺ over a distance of ∼26 Å. Ca²⁺ promotes formation of a [Ca₄ S100 Ax₂] complex, where the Ax peptides are accommodated between helices III/IV and III'/IV'. …

Feasibility Of Laser-Induced Breakdown Spectroscopy (Libs) As An At-Line Validation Tool For Calcium Determination In Infant Formula, Xavier Cama-Moncunill, Maria Markiewicz-Keszycka, Yash Dixit, Raquel Cama-Moncunill, Maria Piedad Casado-Gavalda, Patrick J. Cullen, Carl Sullivan

Articles

In this study, a 150 mJ laser-induced breakdown spectroscopy (LIBS) system was assessed to determine calcium content in infant formula (IF) samples. LIBS is a promising emission spectroscopic technique for elemental analysis, which offers advantages over conventional methods such as real-time analyses, little to no sample preparation and ease of use. The aim of this work was to evaluate the feasibility of LIBS as an at-line tool for IF manufacturing. To this end, IF mixtures with varying content of calcium were prepared over a range (approx. 1.5–7 mg/g of calcium) selected to be in conformity with the guidelines provided by …

Chemical Biology-Based Probes For The Labeling Of Targets On Live Cells, Amanda M. Hussey

Doctoral Dissertations

Proper detection is the key to studying any processes on the cellular scale. Nowhere is this more evident than in the tight space which confines the synaptic cleft. Being able to ascertain the location of receptors on live neurons is fundamental to our understanding of not only how these receptors interact and move inside the cell but also how neurons function. Most detection methods rely on significantly altering the receptor; both tagging with a fluorescent protein or targeting the receptor by a fluorescent reporter in the form of a small molecule causes significant difficulties. These localization techniques often result in …

Direct Determination Of Multiple Ligand Interactions With The Extracellular Domain Of The Calcium Sensing Receptor, Chen Zhang, You Zhuo, Heather A. Moniz, Shuo Wang, Kelley W. Moremen, James H. Prestegard, Edward M. Brown, Jenny J. Yang

Chemistry Faculty Publications

Numerous in vivo functional studies have indicated that the dimeric extracellular domain (ECD) of the CaSR plays a crucial role in regulating Ca2+ homeostasis by sensing Ca2+ and L-Phe. However, direct interaction of Ca2+ and Phe with the receptor’s ECD and the resultant impact on its structure and associated conformational changes have been hampered by the large size of the ECD, its high degree of glycosylation, and the lack of biophysical methods to monitor weak interactions in solution. In the present study, we purified the glycosylated extracellular domain of CaSR (ECD) (residues 20~612), containing either complex or high mannose N-glycan …

Heart Failure And Design Of Potentially Therapeutic Mutants Relieving Serca Inhibition: Expression And Analysis Of Phospholamban Mutants, Kristina R. Poss

Antonian Scholars Honors Program

The CDC identifies heart disease as the leading cause of death in the U.S., and current treatments have variable success. Gene therapy is being investigated as an additional treatment option for heart disease. Various targets impacting calcium ion cycling and by consequence, cardiac contractility, are being studied as options for gene therapy. One molecular target in particular is the protein phospholamban (PLN), which is a small, hydrophobic protein located in the sarcoplasmic reticulum membrane of cardiac muscle, that has been linked to heart failure. Here, four PLN mutants were rationally designed, aiming for optimizing therapeutic potential. These mutants were analyzed …

Structural Basis For Ca 2+-Induced Activation And Dimerization Of Estrogen Receptor Alpha By Calmodulin, Yonghong Zhang, Zhigang Li, David B. Sacks, James B. Ames

Chemistry Faculty Publications and Presentations

The estrogen receptor α (ER-α) regulates expression of target genes implicated in development, metabolism, and breast cancer. Calcium-dependent regulation of ER-α is critical for activating gene expression and is controlled by calmodulin (CaM). Here, we present the NMR structures for the two lobes of CaM each bound to a localized region of ER-α (residues 287–305). A model of the complete CaM·ER-α complex was constructed by combining these two structures with additional data. The two lobes of CaM both compete for binding at the same site on ER-α (residues 292, 296, 299, 302, and 303), which explains why full-length CaM binds …

Organic Materials As Templates For The Formation Of Mesoporous Inorganic Materials And Ordered Inorganic Nanocomposites, Christopher Ryan Ziegler

Open Access Dissertations

Hierarchically structured inorganic materials are everywhere in nature. From unicellular aquatic algae such as diatoms to the bones and/or cartilage that comprise the skeletal systems of vertebrates. Complex mechanisms involving site-specific chemistries and precision kinetics are responsible for the formation of such structures. In the synthetic realm, reproduction of even the most basic hierarchical structure effortlessly produced in nature is difficult. However, through the utilization of self-assembling structures or "templates", such as polymers or amphiphilic surfactants, combined with some favorable interaction between a chosen inorganic, the potential exists to imprint an inorganic material with a morphology dictated via synthetic molecular …

Tuning Calcium Bindging Affinities With Related Biological Functions Of Calmodulin And Designing Protein Based Contrast Agent, Jie Jiang

Chemistry Dissertations

Calmodulin (CaM) is a ubiquitous intracellular protein that regulates biological activities of numerous enzymes and ion channels. Upon responding Ca²⁺ concentration change, Ca²⁺- dependent CaM activates the hydrolyzation of cGMP by PDE and Ca²⁺ releasing channel activity of ryanodine receptor. In this dissertation, a series of CaM variants were engineered to enhance Ca²⁺ binding affinities by increasing the number of negative charged residues in individual EF-hand. The capability of shifting the biphasic Ca²⁺-activation profile of RyR1 is significantly altered by changing Ca²⁺ binding affinity of CaM at the C-terminal. This indicates that …

Defining A Molecular Mechanism For Lead Toxicity Via Calcium-Binding Proteins, Michael Kirberger

Chemistry Dissertations

Essential metals like Ca²⁺ and Zn²⁺ play critical roles in biological processes through protein interactions. Conversely, non-essential metals (e.g., Gd³⁺ and Pb²⁺) also interact with proteins, often with toxic effects. Molecular metal toxicity is assumed to be due to ionic displacement, and studies have demonstrated that Pb²⁺ replaces Zn²⁺, Ca²⁺ and other essential metals in proteins. The focus of this work was to compare protein Ca²⁺ and Pb²⁺ -binding sites and to investigate a mechanism of Pb²⁺ toxicity in Ca²⁺-binding proteins, particularly the intracellular trigger protein …

Effect Of Nanoparticle Surface Charge At The Plasma Membrane And Beyond, Rr Arvizo, Or Miranda, Ma Thompson, Cm Pabelick, R Bhattacharya, Jd Robertson, Vm Rotello, Ys Prakash, P Mukherjee

Vincent Rotello

Herein, we demonstrate that the surface charge of gold nanoparticles (AuNPs) plays a critical role in modulating membrane potential of different malignant and nonmalignant cell types and subsequent downstream intracellular events. The findings presented here describe a novel mechanism for cell-nanoparticle interactions and AuNP uptake: modulation of membrane potential and its effect on intracellular events. These studies will help understand the biology of cell-nanoparticle interactions and facilitate the engineering of nanoparticles for specific intracellular targets.

Ionic Selectivity In L-Type Calcium Channels By Electrostatics And Hard-Core Repulsion, Dezso Boda, Douglas Henderson, Monika Valisko, Bob Eisenberg, Dirk Gillespie

Faculty Publications

A physical model of selective "ion binding" in the L-type calcium channel is constructed, and consequences of the model are compared with experimental data. This reduced model treats only ions and the carboxylate oxygens of the EEEE locus explicitly and restricts interactions to hard-core repulsion and ion–ion and ion–dielectric electrostatic forces. The structural atoms provide a flexible environment for passing cations, thus resulting in a self-organized induced-fit model of the selectivity filter. Experimental conditions involving binary mixtures of alkali and/or alkaline earth metal ions are computed using equilibrium Monte Carlo simulations in the grand canonical ensemble. The model pore rejects …

Determining The Site Specific Metal Binding And Structural Properties Of Ef-Hand Protein Using Grafting Approach, Hsiau-Wei Lee

Chemistry Dissertations

Calmodulin is an essential EF-hand protein with a helix-loop-helix calcium binding motif. Understanding Ca(II) dependent activation of calmodulin and other EF-hand proteins is limited by Ca(II)-induced conformational change, multiple and cooperative binding of Ca(II) ions, and interactions between the paired EF-hand motifs. The goal of this research project is to probe key determinants for calcium binding properties and pairing interactions at the site specific level using a grafting approach and high resolution NMR. An individual Ca(II) binding site of the EF-hand motifs of calmodulin was grafted into a non-calcium dependent protein, CD2, to bypass limitations associated with natural EF-hand proteins …

Rational Design Of Calcium Biosensors, April L. Ellis

Chemistry Dissertations

Understanding the temporal and spatial changes in calcium concentration has been a difficult endeavor for many years due to the relatively small changes in calcium concentration during messenging events, the rapid changes upon physiological messenging, and the unavailability of fast, efficient, and sensitive sensors to detect calcium changes. In addition, the key factors in calcium binding have yet to be determined due to the metal-metal interactions, cooperativity, and conformational change involved in calcium binding to natural calcium-binding proteins. To overcome these obstacles and to engineer calcium sensors for in vivo studies of calcium signaling events, calcium binding sites have been …

Exploring The Role Of Calcium Ions In Biological Systems By Computational Prediction And Protein Engineering, Yubin Zhou

Chemistry Dissertations

Ca2+, a signal for death and life, is closely involved in the regulation of numerous important cellular events. Ca2+ carries out its function through its binding to Ca2+-receptors or Ca2+-binding proteins. The EF-hand protein, with a helix-loop-helix Ca2+-binding motif, constitutes one of the largest protein families. To facilitate our understanding of the role of Ca2+ in biological systems (denoted as calciomics) using genomic information, an improved pattern search method (http://www.chemistry.gsu.edu/faculty/Yang/Calciomics.htm) for the identification of EF-hand and EF-like Ca2+-binding proteins was developed. This fast and robust method allows us to analyze putative EF-hand proteins at the genome-wide level and further visualize …

The Effect Of Protein Dielectric Coefficient On The Ionic Selectivity Of A Calcium Channel, Douglas Henderson, Dezso Boda, Monika Valisko, Bob Eisenberg, Wolfgang Nonner, Dirk Gillespie

Faculty Publications

Calcium-selective ion channels are known to have carboxylate-rich selectivity filters, a common motif that is primarily responsible for their high Ca2+ affinity. Different Ca2+ affinities ranging from micromolar (the L-type Ca channel) to millimolar (the ryanodine receptor channel) are closely related to the different physiological functions of these channels. To understand the physical mechanism for this range of affinities given similar amino acids in their selectivity filters, we use grand canonical Monte Carlo simulations to assess the binding of monovalent and divalent ions in the selectivity filter of a model Ca channel. We use a reduced model where the electrolyte …

Determination Of ^{90}Sr Accumulation In Human Teeth, Recep Acar, Orhan Acar

Turkish Journal of Chemistry

The accumulation of ^{90}Sr in decayed or exfoliated human teeth was investigated by ultra low level beta counting. Fuming nitric acid and the necessary carriers and reagents were used for dissolving the samples, and the separation and purification of ^{90}Sr. The Ca contents of samples were determined by flame atomic absorption spectrometry with Zeeman-effect background correction. A mixture of K and La used as a matrix modifier was found to be preferable for the determination of Ca in samples. The optimum concentration and concentration ratio of K and La on the absorbance of Ca in the NIST certified reference material, …

Determination Of Calcium, Magnesium And Strontium In Soils By Flow Injection Flame Atomic Absorption Spectrometry, Z Arslan, Jf Tyson

Chemistry Department Faculty Publication Series

No abstract provided.

The Removal Hcl From Hot Gases With Calcium Compounds, Qian Lao

Theses

The use of CaCO₃, Ca(OH)₂, and CaO as adsorbents for removal of HCl from hot gas streams is investigated through a series of experiments. The experiments are conducted to evaluate the influence of key parameters such as temperature, (500 K to 1000 K), particle size, (0.037 mm to 3.36 mm), pressure drop of the packed bed, (0.1 cm H₂O to 25.5 cm H₂O), and concentration of CCl in the feed gas, (1,550 ppm to 20,000 ppm), on HCl adsorption. The results of these experiments show that all three of the calcium compound …

Flow-Injection Atomic Spectrometry: A New Analytical Technique, Julian Tyson, S. R. Bysouth, Ea Grzeszczyk, Ebenezer Debrah

Chemistry Department Faculty Publication Series

No abstract provided.

Choosing A Calcium Supplement For Sheep Fed Cereal Grains, R L. Peet, Michael Hare

Journal of the Department of Agriculture, Western Australia, Series 4

Sheep fed cereal grains as an energy source over summer usually need added calcium because cereal grains are generally low in calcium (for example, 0.03 per cent calcium compared to 0.26 per cent phosphorus), and there may not be a natural source such as clover, weeds, leafy stubble or edible bush in the paddock.

The safestt and most effective calcium supplement is finely ground limestone added to the feed, but some farmers have used other sources of calcium such as gypsum and superphosphate in this manner.

Flow-Injection Techniques For The Removal Of Stable-Compound Interferences In Flame Atomic Absorption Spectrometry Of Calcium, C. E. Adeeyinwo, Julian Tyson

Chemistry Department Faculty Publication Series

No abstract provided.

Synthesis Of Potential Long Acting Calcium Channel Antagonists: A Study Of 1,4-Dihydropyridine Analogs, Thomas E. Christos

Chemistry & Biochemistry Theses & Dissertations

An investigation was undertaken to synthesize and evaluate longer acting analogs to the antihypertensive agent nifedipine. Analogs that are capable of covalent bonding to the nifedipine receptor were considered. These compounds may show increased activity as they will remain at the receptor for a longer period of time.

During the course of this study, previously unreported and unexpected products were encountered and lead to a more intense examination of the Hantzsch synthesis. Of particular interest was the oxazolidine 25 which was a major component of the Hantzsch synthesis when ethanolamine was used instead of ammonium hydroxide. Also isolated during this …