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Full-Text Articles in Physical Sciences and Mathematics
Measurement Of Anti-Cancer Agent Methoxyamine In Plasma By Tandem Mass Spectrometry With On-Line Sample Extraction, Shuming Yang, Lili Liu, Stanton L. Gerson, Yan Xu
Measurement Of Anti-Cancer Agent Methoxyamine In Plasma By Tandem Mass Spectrometry With On-Line Sample Extraction, Shuming Yang, Lili Liu, Stanton L. Gerson, Yan Xu
Chemistry Faculty Publications
In this work, we present the development and validation of a tandem mass spectrometry method for the quantitative determination of methoxyamine (CH3ONH2), a potential new chemotherapeutic agent, in human and mouse plasma. Methoxyamine together with the internal standard (I.S.) methoxyl-D3-amine was directly derivatized in plasma sample with a novel chemical agent 4-(N,N-diethylamino)benzaldehyde. The product solution was injected into an on-line Oasis® HLB extraction column ( mm) for analyte extraction. After the elution of extractives, the derivatized analytes were monitored by the positive-electrospray-ionization mass spectrometry (ESI-MS-MS). The structures of derivatized analytes were elucidated by fragmentation. Quantitation of plasma methoxyamine was carried …
Structural Requirements For Expression Of Factor Va Activity, Michael Kalafatis, Daniel O. Beck, Kenneth G. Mann
Structural Requirements For Expression Of Factor Va Activity, Michael Kalafatis, Daniel O. Beck, Kenneth G. Mann
Chemistry Faculty Publications
Thrombin activated factor Va (factor VIIa, residues 1-709 and 1546-2196) has an apparent dissociation constant (Kd,app) for factor Xa within prothrombinase of approximately 0.5 nM. A protease (NN) purified from the venom of the snake Naja nigricollis nigricollis, cleaves human factor V at Asp697, Asp1509, and Asp1514 to produce a molecule (factor VNN) that is composed of a Mr 100,000 heavy chain (amino acid residues 1-696) and a Mr 80,000 light chain (amino acid residues 1509/1514-2196). Factor VNN, has a Kd,app for factor Xa of 4 nm and reduced clotting activity. Cleavage of factor VIIa by NN at Asp697 results …
Amino Acids Glu323, Tyr324, Glu330, And Val331 Of Factor Va Heavy Chain Are Essential For Expression Of Cofactor Activity, Lisam S. Singh, Michael A. Bukys, Daniel O. Beck, Michael Kalafatis
Amino Acids Glu323, Tyr324, Glu330, And Val331 Of Factor Va Heavy Chain Are Essential For Expression Of Cofactor Activity, Lisam S. Singh, Michael A. Bukys, Daniel O. Beck, Michael Kalafatis
Chemistry Faculty Publications
We have recently demonstrated that amino acid region 323-331 of factor Va heavy chain (9 amino acids, AP4') contains a binding site for factor Xa (Kalafatis, M., and Beck, D. O. (2002) Biochemistry 41, 12715-12728). To ascertain which amino acids within this region are important for the effector and receptor properties of the cofactor with respect to factor Xa, we have synthesized three overlapping peptides (5 amino acids each) spanning the amino acid region 323-331 and tested them for their effect on prothrombinase complex assembly and function. Peptide containing amino acids 323EYFIA327 alone was found to increase the catalytic efficiency …
Rnase L Mediates Transient Control Of The Interferon Response Through Modulation Of The Double-Stranded Rna-Dependent Protein Kinase Pkr, Khalid S.A. Khabar, Yunus M. Siddiqui, Fahad Al-Zoghaibi, Latifa Al-Haj, Mohammed Dhalla, Aimin Zhou, Beihua Dong, Mark Whitmore, Jayashree Paranjape, Mohammed N. Al-Ahdal, Futwan Al-Mohanna, Bryan R.G. Williams, Robert H. Silverman
Rnase L Mediates Transient Control Of The Interferon Response Through Modulation Of The Double-Stranded Rna-Dependent Protein Kinase Pkr, Khalid S.A. Khabar, Yunus M. Siddiqui, Fahad Al-Zoghaibi, Latifa Al-Haj, Mohammed Dhalla, Aimin Zhou, Beihua Dong, Mark Whitmore, Jayashree Paranjape, Mohammed N. Al-Ahdal, Futwan Al-Mohanna, Bryan R.G. Williams, Robert H. Silverman
Chemistry Faculty Publications
The transient control of diverse biological responses that occurs in response to varied forms of stress is often a highly regulated process. During the interferon (IFN) response, translational repression due to phosphorylation of eukaryotic initiation factor 2α, eIF2α, by the double-stranded RNA-dependent protein kinase, PKR, constitutes a means of inhibiting viral replication. Here we show that the transient nature of the IFN response against acute viral infections is regulated, at least in part, by RNase L. During the IFN antiviral response in RNase L-null cells, PKR mRNA stability was enhanced, PKR induction was increased, and the phosphorylated form of eIF2α …
Evaluating The Effects Of Enhanced Processivity And Metal Ions On Translesion Dna Replication Catalyzed By The Bacteriophage T4 Dna Polymerase, Edmunds Z. Reineks, Anthony J. Berdis
Evaluating The Effects Of Enhanced Processivity And Metal Ions On Translesion Dna Replication Catalyzed By The Bacteriophage T4 Dna Polymerase, Edmunds Z. Reineks, Anthony J. Berdis
Chemistry Faculty Publications
The fidelity of DNA replication is achieved in a multiplicative process encompassing nucleobase selection and insertion, removal of misinserted nucleotides by exonuclease activity, and enzyme dissociation from primer/templates that are misaligned due to mispairing. In this study, we have evaluated the effect of altering these kinetic processes on the dynamics of translesion DNA replication using the bacteriophage T4 replication apparatus as a model system. The effect of enhancing the processivity of the T4 DNA polymerase, gp43, on translesion DNA replication was evaluated using a defined in vitro assay system. While the T4 replicase (gp43 in complex with gp45) can perform …
The Solvent Boundary Potential: A New Approach For Computer Simulation Of Large Systems, Valentin Gogonea
The Solvent Boundary Potential: A New Approach For Computer Simulation Of Large Systems, Valentin Gogonea
Chemistry Faculty Publications
The paper presents the theoretical framework for the development of a new solvent boundary method for computer simulations and its possible application to the simulation of nitric oxide synthase. Different approaches for the construction of a solvent boundary potential are reviewed and their strengths and weaknesses are discussed. A new solvent boundary potential is proposed which combines the mean field force approximation with the Green's function approach for treating long-range electrostatic interactions, and introduces a novel strategy to treat electrostriction effects due to ions crossing the solvent boundary. Finally, a series of computational tests are devised in order to assess …
Measurement Of The Anti-Cancer Agent Gemcitabine In Human Plasma By High-Performance Liquid Chromatography, Bruce Keith, Yan Xu, Jean L. Grem
Measurement Of The Anti-Cancer Agent Gemcitabine In Human Plasma By High-Performance Liquid Chromatography, Bruce Keith, Yan Xu, Jean L. Grem
Chemistry Faculty Publications
A reversed-phase HPLC assay has been developed to determine the concentration of the anti-metabolite 2′,2′-difluorodeoxycytidine (gemcitabine, dFdC) in human plasma over the concentration range of 0.5–150 μM (0.13–39.44 μg/ml), and 2′,2′-difluorodeoxyuridine (dFdU), the deaminated, inactive metabolite, over the range of 1.0–227 μM (0.26–60 μg/ml). After the addition of 20 nmol 2′-fluorodeoxycytidine (FdC) as an internal standard, 0.5-ml samples of plasma were subjected to acetonitrile precipitation, followed by analysis using a gradient reversed-phase HPLC assay with UV detection. A Phenomenex Columbus™ C18 column, 5 μm, 150×4.6 mm, and a Waters C18, 4 μm, Nova-Pak Sentry guard column were used to achieve …
Examination Of The Role Of The Clamp-Loader And Atp Hydrolysis In The Formation Of The Bacteriophage T4 Polymerase Holoenzyme, Michael A. Trakselis, Anthony J. Berdis, Stephen J. Benkovic
Examination Of The Role Of The Clamp-Loader And Atp Hydrolysis In The Formation Of The Bacteriophage T4 Polymerase Holoenzyme, Michael A. Trakselis, Anthony J. Berdis, Stephen J. Benkovic
Chemistry Faculty Publications
Transient kinetic analyses further support the role of the clamp-loader in bacteriophage T4 as a catalyst which loads the clamp onto DNA through the sequential hydrolysis of two molecules of ATP before and after addition of DNA. Additional rapid-quench and pulse-chase experiments have documented this stoichiometry. The events of ATP hydrolysis have been related to the opening/closing of the clamp protein through fluorescence resonance energy transfer (FRET). In the absence of a hydrolysable form of ATP, the distance across the subunit interface of the clamp does not increase as measured by intramolecular FRET, suggesting gp45 cannot be loaded onto DNA. …
Synthesis And Potential Antimetastatic Activity Of Monovalent And Divalent Β-D-Galactopyranosyl-(1→4)-2-Acetamido-2-Deoxy-D-Glucopyranosides, Qin Li, Bin Su, Hui Li, Xiang Bao Meng, Meng Shen Cai, Zhong Jun Li, Rou Li Zhou, Ta Lin Suo
Synthesis And Potential Antimetastatic Activity Of Monovalent And Divalent Β-D-Galactopyranosyl-(1→4)-2-Acetamido-2-Deoxy-D-Glucopyranosides, Qin Li, Bin Su, Hui Li, Xiang Bao Meng, Meng Shen Cai, Zhong Jun Li, Rou Li Zhou, Ta Lin Suo
Chemistry Faculty Publications
Anomers of monovalent and divalent β-d-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-d-gluco-pyranosides were synthesized under different glycosylation conditions, and evaluated for in vitro antimetastatic activity. Three compounds showed promising inhibitory effects on cancer cell attachment, spreading, migration, and invasion. Six divalent O-β-d-galactopyranosyl-(1→4)-2-acetamido-2-deoxy-d-glucopyranosides (29–34) were synthesized and their antimetastatic activities were studied.
Liquid Chromatography–Mass Spectrometry Method For The Analysis Of The Anti-Cancer Agent Capecitabine And Its Nucleoside Metabolites In Human Plasma, Yan Xu, Jean L. Grem
Liquid Chromatography–Mass Spectrometry Method For The Analysis Of The Anti-Cancer Agent Capecitabine And Its Nucleoside Metabolites In Human Plasma, Yan Xu, Jean L. Grem
Chemistry Faculty Publications
A reversed-phase high-performance liquid chromatography method with electrospray ionization and mass spectral detection is described for the determination of capecitabine, 5′-deoxy-5-fluorocytidine and 5′-deoxy-5-fluorouridine in human plasma with 5-chloro-2′-deoxyuridine as the internal standard. An on-line sample clean-up procedure allows dilution of the plasma sample with the initial mobile phase. The linear dynamic range is 0.0500–10.0 μg/ml for capecitabine, and 0.0500–25.0 μg/ml for the metabolites, 5′-deoxy-5-fluorocytidine and 5′-deoxy-5-fluorouridine, respectively. This method has been used to analyze plasma samples from patients receiving capecitabine in combination with oxaliplatin.
A Phase I And Pharmacologic Study Of Weekly Gemcitabine In Combination With Infusional 5-Fluorodeoxyuridine And Oral Calcium Leucovorin, Jean L. Grem, Mary G. Quinn, Bruce Keith, Brian P. Monahan, J. Michael Hamilton, Yan Xu, Nancy Harold, Dat Nguyen, Chris H. Takimoto, Anthony Rowedder, Janet Pang, Geraldine Morrison, Alice Chen
A Phase I And Pharmacologic Study Of Weekly Gemcitabine In Combination With Infusional 5-Fluorodeoxyuridine And Oral Calcium Leucovorin, Jean L. Grem, Mary G. Quinn, Bruce Keith, Brian P. Monahan, J. Michael Hamilton, Yan Xu, Nancy Harold, Dat Nguyen, Chris H. Takimoto, Anthony Rowedder, Janet Pang, Geraldine Morrison, Alice Chen
Chemistry Faculty Publications
Purpose: Since preclinical studies have shown more than additive cytotoxicity and DNA damage with the combination of gemcitabine and 5-fluoro-2′-deoxyuridine (FUDR), we studied this combination in a phase I trial. Methods: Gemcitabine alone was given in cycle 1 as a 24-h, 2-h or 1-h i.v. infusion weekly for 3 of 4 weeks; if tolerated, a 24-h i.v. infusion of FUDR was added with oral leucovorin. The cycle was aborted for grade 3 thrombocytopenia, grade 4 neutropenia, and grade 2 or worse nonhematologic toxicity. Results: During cycle 1, six of eight patients who received 150 or 100 mg/m2 over 24 h …