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Cleveland State University

Chemistry Faculty Publications

Series

2013

Articles 1 - 18 of 18

Full-Text Articles in Physical Sciences and Mathematics

Amino Acid Region 1000–1008 Of Factor V Is A Dynamic Regulator For The Emergence Of Procoagulant Activity, Joesph R. Wiencek, Mahesheema Na, Jamila Hirbawi, Michael Kalafatis Dec 2013

Amino Acid Region 1000–1008 Of Factor V Is A Dynamic Regulator For The Emergence Of Procoagulant Activity, Joesph R. Wiencek, Mahesheema Na, Jamila Hirbawi, Michael Kalafatis

Chemistry Faculty Publications

Single chain factor V (fV) circulates as an Mr 330,000 quiescent pro-cofactor. Removal of the B domain and generation of factor Va (fVa) are vital for procoagulant activity. We investigated the role of the basic amino acid region 1000-1008 within the B domain of fV by constructing a recombinant mutant fV molecule with all activation cleavage sites (Arg(709)/Arg(1018)/Arg(1545)) mutated to glutamine (fV(Q3)), a mutant fV molecule with region 1000-1008 deleted (fV(ΔB9)), and a mutant fV molecule containing the same deletion with activation cleavage sites changed to glutamine (fV(ΔB9/Q3)). The recombinant molecules along with wild type fV (fV(WT)) were transiently expressed …

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Lack Of Rnase L Attenuates Macrophage Functions, Xin Yi, Chun Zeng, Hongli Liu, Xiaoli Chen, Ping Zhang, Boo Seok Yun, Ge Jin, Aimin Zhou Dec 2013

Lack Of Rnase L Attenuates Macrophage Functions, Xin Yi, Chun Zeng, Hongli Liu, Xiaoli Chen, Ping Zhang, Boo Seok Yun, Ge Jin, Aimin Zhou

Chemistry Faculty Publications

Background: Macrophages are one of the major cell types in innate immunity against microbial infection. It is believed that the expression of proinflammatory genes such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β, IL–6, and cyclooxygenase-2 (Cox-2) by macrophages is also crucial for activation of both innate and adaptive immunities. RNase L is an interferon (IFN) inducible enzyme which is highly expressed in macrophages. It has been demonstrated that RNase L regulates the expression of certain inflammatory genes. However, its role in macrophage function is largely unknown. Methodology: Bone marrow-derived macrophages (BMMs) were generated from RNase L+/+and −/− mice. The migration …

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Can Inhibitor-Resistant Substitutions In The Mycobacterium Tuberculosis Β-Lactamase Blac Lead To Clavulanate Resistance?: A Biochemical Rationale For The Use Of Β-Lactam–Β-Lactamase Inhibitor Combinations, Sebastian G. Kurz, Kerstin A. Wolff, Saugata Hazra, Christopher R. Bethel, Andrea M. Hujer, Kerri M. Smith, Yan Xu, Lee W. Tremblay, John S. Blanchard, Liem Nguyen, Robert A. Bonomo Dec 2013

Can Inhibitor-Resistant Substitutions In The Mycobacterium Tuberculosis Β-Lactamase Blac Lead To Clavulanate Resistance?: A Biochemical Rationale For The Use Of Β-Lactam–Β-Lactamase Inhibitor Combinations, Sebastian G. Kurz, Kerstin A. Wolff, Saugata Hazra, Christopher R. Bethel, Andrea M. Hujer, Kerri M. Smith, Yan Xu, Lee W. Tremblay, John S. Blanchard, Liem Nguyen, Robert A. Bonomo

Chemistry Faculty Publications

The current emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis calls for novel treatment strategies. Recently, BlaC, the principal β-lactamase of Mycobacterium tuberculosis, was recognized as a potential therapeutic target. The combination of meropenem and clavulanic acid, which inhibits BlaC, was found to be effective against even extensively drug-resistant M. tuberculosis strains when tested in vitro. Yet there is significant concern that drug resistance against this combination will also emerge. To investigate the potential of BlaC to evolve variants resistant to clavulanic acid, we introduced substitutions at important amino acid residues of M. tuberculosis BlaC (R220, A244, S130, and …

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Cyclometalated Iridium(Iii) Complexes With Deoxyribose Substituents, Ayan Maity, Jung-Suk Choi, Thomas S. Teets, Nihal Deligonul, Anthony J. Berdis, Thomas G. Gray Nov 2013

Cyclometalated Iridium(Iii) Complexes With Deoxyribose Substituents, Ayan Maity, Jung-Suk Choi, Thomas S. Teets, Nihal Deligonul, Anthony J. Berdis, Thomas G. Gray

Chemistry Faculty Publications

Fundamental study of enzymatic nucleoside transport suffers for lack of optical probes that can be tracked noninvasively. Nucleoside transporters are integral membrane glycoproteins that mediate the salvage of nucleosides and their passage across cell membranes. The substrate recognition site is the deoxyribose sugar, often with little distinction among nucleobases. Reported here are nucleoside analogues in which emissive, cyclometalated iridium(III) complexes are “clicked” to C-1 of deoxyribose in place of canonical nucleobases. The resulting complexes show visible luminescence at room temperature and 77 K with microsecond-length triplet lifetimes. A representative complex is crystallographically characterized. Transport and luminescence are demonstrated in cultured …

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Function And Distribution Of Apolipoprotein A1 In The Artery Wall Are Markedly Distinct From Those In Plasma, Joseph A. Didonato, Ying Huang, Kulwant S. Aulak, Orli Even-Or, Gary Gerstenecker, Valentin Gogonea, Yuping Wu, Paul L. Fox, W.H. Wilson Tang, Edward F. Plow, Jonathan D. Smith, Edward A. Fisher, Stanley L. Hazen Oct 2013

Function And Distribution Of Apolipoprotein A1 In The Artery Wall Are Markedly Distinct From Those In Plasma, Joseph A. Didonato, Ying Huang, Kulwant S. Aulak, Orli Even-Or, Gary Gerstenecker, Valentin Gogonea, Yuping Wu, Paul L. Fox, W.H. Wilson Tang, Edward F. Plow, Jonathan D. Smith, Edward A. Fisher, Stanley L. Hazen

Chemistry Faculty Publications

Background—Prior studies show that apolipoprotein A1 (apoA1) recovered from human atherosclerotic lesions is highly oxidized. Ex vivo oxidation of apoA1 or high-density lipoprotein (HDL) cross-links apoA1 and impairs lipid binding, cholesterol efflux, and lecithin-cholesterol acyltransferase activities of the lipoprotein. Remarkably, no studies to date directly quantify either the function or HDL particle distribution of apoA1 recovered from the human artery wall. Methods and Results—A monoclonal antibody (10G1.5) was developed that equally recognizes lipid-free and HDL-associated apoA1 in both native and oxidized forms. Examination of homogenates of atherosclerotic plaque–laden aorta showed >100-fold enrichment of apoA1 compared with normal aorta (P<0.001). Surprisingly, buoyant density fractionation revealed that only a minority (<3% of total) of apoA1 recovered from either lesions or normal aorta resides within an HDL-like particle (1.063≤d≤1.21). In contrast, the majority (>90%) …

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Myeloperoxidase, Paraoxonase-1, And Hdl Form A Functional Ternary Complex, Ying Huang, Zhiping Wu, Meliana Riwanto, Shengqiang Gao, Bruce S. Levison, Xiaodong Gu, Xiaoming Fu, Matthew A. Wagner, Christian Besler, Gary Gerstenecker, Renliang Zhang, Xin Min Li, Anthony J. Didonato, Valentin Gogonea, W.H. Wilson Tang, Jonathan D. Smith, Edward F. Plow, Paul L. Fox, Diana M. Shih, Aldons J. Lusis, Edward A. Fisher, Joseph A. Didonato, Ulf Landmesser, Stanley L. Hazen Sep 2013

Myeloperoxidase, Paraoxonase-1, And Hdl Form A Functional Ternary Complex, Ying Huang, Zhiping Wu, Meliana Riwanto, Shengqiang Gao, Bruce S. Levison, Xiaodong Gu, Xiaoming Fu, Matthew A. Wagner, Christian Besler, Gary Gerstenecker, Renliang Zhang, Xin Min Li, Anthony J. Didonato, Valentin Gogonea, W.H. Wilson Tang, Jonathan D. Smith, Edward F. Plow, Paul L. Fox, Diana M. Shih, Aldons J. Lusis, Edward A. Fisher, Joseph A. Didonato, Ulf Landmesser, Stanley L. Hazen

Chemistry Faculty Publications

Myeloperoxidase (MPO) and paraoxonase 1 (PON1) are high-density lipoprotein–associated (HDL-associated) proteins mechanistically linked to inflammation, oxidant stress, and atherosclerosis. MPO is a source of ROS during inflammation and can oxidize apolipoprotein A1 (APOA1) of HDL, impairing its atheroprotective functions. In contrast, PON1 fosters systemic antioxidant effects and promotes some of the atheroprotective properties attributed to HDL. Here, we demonstrate that MPO, PON1, and HDL bind to one another, forming a ternary complex, wherein PON1 partially inhibits MPO activity, while MPO inactivates PON1. MPO oxidizes PON1 on tyrosine 71 (Tyr71), a modified residue found in human atheroma that is critical for …

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Thermodynamic Characterization Of Five Key Kinetic Parameters That Define Neuronal Nitric Oxide Synthase Catalysis, Mohammad Mahfuzul Haque, Jesus Tejero, Mekki Bayachou, Zhi-Qiang Wang, Mohammed Fadlalla, Dennis J. Stuehr Sep 2013

Thermodynamic Characterization Of Five Key Kinetic Parameters That Define Neuronal Nitric Oxide Synthase Catalysis, Mohammad Mahfuzul Haque, Jesus Tejero, Mekki Bayachou, Zhi-Qiang Wang, Mohammed Fadlalla, Dennis J. Stuehr

Chemistry Faculty Publications

NO synthase (NOS) enzymes convert L-arginine to NO in two sequential reactions whose rates (kcat1 and kcat2) are both limited by the rate of ferric heme reduction (kr). An enzyme ferric heme –NO complex forms as an immediate product complex and then undergoes either dissociation (at a rate that we denote as kd) to release NO in a productive manner, or reduction (kr) to form a ferrous heme –NO complex that must react with O2 (at a rate that we denote as kox) in a NO dioxygenase reaction that regenerates the ferric enzyme. The interplay of these five kinetic parameters …

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A Phase 1 Study Of Trc102, An Inhibitor Of Base Excision Repair, And Pemetrexed In Patients With Advanced Solid Tumors, Michael S. Gordon, Lee S. Rosen, David Mendelson, Ramesh K. Ramanathan, Jonathan Goldman, Lili Liu, Yan Xu, Stanton L. Gerson, Stephen P. Anthony, William D. Figg, Shawn Spencer, Bonne J. Adams, Charles P. Theuer, Bryan R. Leigh, Glen J. Weiss Jun 2013

A Phase 1 Study Of Trc102, An Inhibitor Of Base Excision Repair, And Pemetrexed In Patients With Advanced Solid Tumors, Michael S. Gordon, Lee S. Rosen, David Mendelson, Ramesh K. Ramanathan, Jonathan Goldman, Lili Liu, Yan Xu, Stanton L. Gerson, Stephen P. Anthony, William D. Figg, Shawn Spencer, Bonne J. Adams, Charles P. Theuer, Bryan R. Leigh, Glen J. Weiss

Chemistry Faculty Publications

Introduction TRC102 potentiates the activity of cancer therapies that induce base excision repair (BER) including antimetabolite and alkylating agents. TRC102 rapidly and covalently binds to apurinic/apyrimidinic (AP) sites generated during BER, and TRC102-bound DNA causes topoisomerase II-dependent irreversible strand breaks and apoptosis. This study assessed the safety, maximum-tolerated dose (MTD), pharmacokinetics and pharmacodynamics of TRC102 alone and in combination with pemetrexed. Purpose Patients with advanced solid tumors received oral TRC102 daily for 4 days. Two weeks later, patients began standard-dose pemetrexed on day 1 in combination with oral TRC102 on days 1 to 4. The pemetrexed-TRC102 combination was repeated every …

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Polymerized Hemin As An Electrocatalytic Platform For Peroxynitrite's Oxidation And Detection, Serban F. Peteu, Tiyash Bose, Mekki Bayachou May 2013

Polymerized Hemin As An Electrocatalytic Platform For Peroxynitrite's Oxidation And Detection, Serban F. Peteu, Tiyash Bose, Mekki Bayachou

Chemistry Faculty Publications

Peroxynitrite (ONOO−) constitutes a major cytotoxic agent, implicated in a host of pathophysiological conditions, thereby stimulating a tremendous interest in evaluating its role as an oxidant in vivo. Some of the detection methods for peroxynitrite include oxidation of fluorescent probes, EPR spectroscopy, chemiluminescence, immunohistochemistry, and probe nitration; however, these are more difficult to apply for real-time quantification due to their inherent complexity. The electrochemical detection of peroxynitrite is a simpler and more convenient technique, but the best of our knowledge there are only few papers to date studying its electrochemical signature, or reporting amperometric microsensors for peroxynitrite. Recently, we have …

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The Low-Resolution Structure Of Nascent High Density Lipoprotein Reconstituted With Dmpc With And Without Cholesterol Reveals A Mechanism For Particle Expansion, Valentin Gogonea, Gary S. Gerstenecker, Zhiping Wu, Xavier Lee, Celalettin Topbas, Matthew A. Wagner, Thomas C. Tallant, Jonathan D. Smith, Phil Callow, Vitaliy Pipich, Helen Malet, Guy Schoehn, Joseph A. Didonato, Stanley L. Hazen Apr 2013

The Low-Resolution Structure Of Nascent High Density Lipoprotein Reconstituted With Dmpc With And Without Cholesterol Reveals A Mechanism For Particle Expansion, Valentin Gogonea, Gary S. Gerstenecker, Zhiping Wu, Xavier Lee, Celalettin Topbas, Matthew A. Wagner, Thomas C. Tallant, Jonathan D. Smith, Phil Callow, Vitaliy Pipich, Helen Malet, Guy Schoehn, Joseph A. Didonato, Stanley L. Hazen

Chemistry Faculty Publications

High density lipoproteins (HDL) are athero-protective particles under investigation as potential therapeutic agents for cardiovascular disease. We applied small angle neutron scattering (SANS) with contrast variation to obtain the low resolution structure of nascent HDL (nHDL) reconstituted with dimyristoyl phosphatidyl choline (DMPC), apoA1:DMPC (1:80, mol:mol). The overall shape of the entire particle is discoidal, with low resolution architecture of apoA1 visualized as an open, contorted, and slightly out of plane structure with three arms, while the low resolution shape of the lipid phase is an oblate ellipsoid that fits well within the protein shape. Modeling studies incorporating the SANS data …

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Insights Into The Roles Of Desolvation And Π-Electron Interactions During Dna Polymerization, Edward A. Motea, Irene Lee, Anthony J. Berdis Mar 2013

Insights Into The Roles Of Desolvation And Π-Electron Interactions During Dna Polymerization, Edward A. Motea, Irene Lee, Anthony J. Berdis

Chemistry Faculty Publications

This report describes the use of several isosteric non-natural nucleotides as probes to evaluate the roles of nucleobase shape, size, solvation energies, and π-electron interactions as forces influencing key kinetic steps of the DNA polymerization cycle. Results are provided using representative high- and low-fidelity DNA polymerases. Results generated with the E. coli Klenow fragment reveal that this high-fidelity polymerase utilizes hydrophobic nucleotide analogues with higher catalytic efficiencies compared to hydrophilic analogues. These data support a major role for nucleobase desolvation during nucleotide selection and insertion. In contrast, the low-fidelity HIV-1 reverse transcriptase discriminates against hydrophobic analogues and only tolerates non-natural …

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Development, Validation And Pilot Screening Of An In Vitro Multi-Cellular Three-Dimensional Cancer Spheroid Assay For Anti-Cancer Drug Testing, Rati Lama, Lin Zhang, Janine M. Naim, Jennifer Williams, Aimin Zhou, Bin Su Feb 2013

Development, Validation And Pilot Screening Of An In Vitro Multi-Cellular Three-Dimensional Cancer Spheroid Assay For Anti-Cancer Drug Testing, Rati Lama, Lin Zhang, Janine M. Naim, Jennifer Williams, Aimin Zhou, Bin Su

Chemistry Faculty Publications

It has been demonstrated that two-dimensional (2D) monolayer cancer cell proliferation assay for anti-cancer drug screening is a very artificial model and cannot represent the characteristics of three-dimensional (3D) solid tumors. The multi-cellular in vitro 3D tumor spheroid model is of intermediate complexity, and can provide a bridge to the gap between the complex in vivo tumors and simple in vitro monolayer cell cultures. In this study, a simple and cost-effective cancer 3D spheroid assay suitable for small molecule anti-cancer compound screening was developed, standardized and validated on H292 non-small lung cancer cell line. A pilot screening with this assay …

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Spectroscopic Analysis Of Polymerization And Exonuclease Proofreading By A High-Fidelity Dna Polymerase During Translesion Dna Synthesis, Babho Devadoss, Irene Lee, Anthony J. Berdis Jan 2013

Spectroscopic Analysis Of Polymerization And Exonuclease Proofreading By A High-Fidelity Dna Polymerase During Translesion Dna Synthesis, Babho Devadoss, Irene Lee, Anthony J. Berdis

Chemistry Faculty Publications

High fidelity DNA polymerases maintain genomic fidelity through a series of kinetic steps that include nucleotide binding, conformational changes, phosphoryl transfer, polymerase translocation, and nucleotide excision. Developing a comprehensive understanding of how these steps are coordinated during correct and pro-mutagenic DNA synthesis has been hindered due to lack of spectroscopic nucleotides that function as efficient polymerase substrates. This report describes the application of a non-natural nucleotide designated 5-naphthyl-indole-2′-deoxyribose triphosphate which behaves as a fluorogenic substrate to monitor nucleotide incorporation and excision during the replication of normal DNA versus two distinct DNA lesions (cyclobutane thymine dimer and an abasic site). Transient …

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Charge-Pairing Interactions Control The Conformational Setpoint And Motions Of The Fmn Domain In Neuronal Nitric Oxide Synthase, Mohammad Mahfuzul Haque, Mekki Bayachou, Mohammed A. Fadlalla, Deborah Durra, Dennis J. Stuehr Jan 2013

Charge-Pairing Interactions Control The Conformational Setpoint And Motions Of The Fmn Domain In Neuronal Nitric Oxide Synthase, Mohammad Mahfuzul Haque, Mekki Bayachou, Mohammed A. Fadlalla, Deborah Durra, Dennis J. Stuehr

Chemistry Faculty Publications

The NOS (nitric oxide synthase; EC 1.14.13.39) enzymes contain a C-terminal flavoprotein domain [NOSred (reductase domain of NOS)] that binds FAD and FMN, and an N-terminal oxygenase domain that binds haem. Evidence suggests that the FMN-binding domain undergoes large conformational motions to shuttle electrons between the NADPH/FAD-binding domain [FNR (ferredoxin NADP-reductase)] and the oxygenase domain. Previously we have shown that three residues on the FMN domain (Glu(762), Glu(816) and Glu(819)) that make charge-pairing interactions with the FNR help to slow electron flux through nNOSred (neuronal NOSred). In the present study, we show that charge neutralization or reversal at each of …

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Synthesis And Evaluation Of Some 17-Acetamidoandrostane And N,N-Dimethyl-7-Deoxycholic Amide Derivatives As Cytotoxic Agents: Structure/Activity Studies, Yanmin Huang, Jianguo Cui, Linyi Jia, Chunfang Gan, Huacan Song, Chun Zeng, Aimin Zhou Jan 2013

Synthesis And Evaluation Of Some 17-Acetamidoandrostane And N,N-Dimethyl-7-Deoxycholic Amide Derivatives As Cytotoxic Agents: Structure/Activity Studies, Yanmin Huang, Jianguo Cui, Linyi Jia, Chunfang Gan, Huacan Song, Chun Zeng, Aimin Zhou

Chemistry Faculty Publications

Using pregnenolone and 7-deoxycholic acid as starting materials, some 17-acetamidoandrostane and N,N-dimethyl-7-deoxycholic amide derivatives were synthesized. The cytotoxicity of the synthesized compounds was tested in vitro against two tumor cell lines: SGC 7901 (human gastric carcinoma) and Bel 7404 (human liver carcinoma). The result showed that the blockage of the interaction of the amide group with outside groups might cause a decrease of the cytotoxicity, and an O-benzyloximino group at the 3-position of N,N-dimethyl-7-deoxycholic amide could enhance the cytotoxic activity of the compound. The information obtained from the studies provides the structure-activity relationship for these compounds and may be useful …

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Metastable Nanostructured Metallized Fluoropolymer Composites For Energetics, Hannah A. Miller, Bradley S. Kusel, Seth T. Danielson, James W. Neat, Eryn K. Avjian, Scott N. Pierson, Stephen M. Budy, David W. Ball, Scott T. Iacono, Sharon C. Kettwich Jan 2013

Metastable Nanostructured Metallized Fluoropolymer Composites For Energetics, Hannah A. Miller, Bradley S. Kusel, Seth T. Danielson, James W. Neat, Eryn K. Avjian, Scott N. Pierson, Stephen M. Budy, David W. Ball, Scott T. Iacono, Sharon C. Kettwich

Chemistry Faculty Publications

Fluoropolymers have long served as potent oxidizers for metal-based pyrolant designs for the preparation of energetic materials. Commercial perfluoropolyethers (PFPEs), specifically known as Fomblins®, are well-known to undergo accelerated thermal degradation in the presence of native metals and Lewis acids producing energetically favorable metal fluoride species. This study employs the use of PFPEs to coat nano-aluminum (n-Al) and under optimized stoichiometric formulations, harness optimized energy output. The PFPEs serve as ideal oxidizers of n-Al because they are non-volatile, viscous liquids that coat the particles thereby maximizing surface interactions. The n-Al/PFPE blended combination is required to interface with an epoxy-based matrix …

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Voltage-Controlled Enzyme-Catalyzed Glucose–Gluconolactone Conversion Using A Field-Effect Enzymatic Detector, Siu Tung Yau, Yan Xu, Yang Song, Ye Feng, Jiapeng Wang Jan 2013

Voltage-Controlled Enzyme-Catalyzed Glucose–Gluconolactone Conversion Using A Field-Effect Enzymatic Detector, Siu Tung Yau, Yan Xu, Yang Song, Ye Feng, Jiapeng Wang

Chemistry Faculty Publications

The field-effect enzymatic detection (FEED) technique was used to control the kinetics of the enzymatic conversion of glucose to gluconolactone. The glucose–gluconolactone conversion occurring at an enzyme-immobilized electrode, a well-studied process, was confirmed using mass spectrometry. Electrochemical studies showed that the glucose oxidation current depends on the gating voltage VG and the ion concentration of the sample solution. Additionally, the depletion of glucose in the sample also showed a dependence on VG. FEED was used to detect H2O2 on the zepto-molar level in order to show the ultrasensitive detection capability of the technique. These results, while providing evidence for the …

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Peroxynitrite Activity Of Hemin-Functionalized Reduced Graphene Oxide, Raluca Oprea, Serban F. Peteu, Palaniappan Subramanian, Wang Qi, Emmanualle Pichonat, Henri Happy, Mekki Bayachou, Rabah Boukherroub, Sabine Szunerits Jan 2013

Peroxynitrite Activity Of Hemin-Functionalized Reduced Graphene Oxide, Raluca Oprea, Serban F. Peteu, Palaniappan Subramanian, Wang Qi, Emmanualle Pichonat, Henri Happy, Mekki Bayachou, Rabah Boukherroub, Sabine Szunerits

Chemistry Faculty Publications

Conducting interfaces modified with reduced graphene oxide (rGO) have shown improved electrochemical response for different analytes. The efficient formation of functionalized rGO based materials is thus of current interest for the development of sensitive and selective biosensors. Herein, we report a simple and environmentally friendly method for the formation of a hemin-functionalized rGO hybrid nanomaterial that exhibits remarkable sensitivity to peroxynitrite (ONOO−) in solution. The hemin-functionalized rGO hybrid nanomaterial was formed by mixing an aqueous solution of graphene oxide (GO) with hemin and sonicating the suspension for 5 h at room temperature. In addition to playing a key role in …

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