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Chemistry

Georgia State University

Chemistry Faculty Publications

Series

2014

Articles 1 - 21 of 21

Full-Text Articles in Physical Sciences and Mathematics

Role Of Ca2+ And L-Phe In Regulating Functional Cooperativity Of Disease- Associated ‘‘Toggle’’ Calcium-Sensing Receptor Mutations, Chen Zhang, Nagaraju Mulpuri, Fadil M. Hannan, M. Andrew Nesbit, Rajesh V. Thakker, Donald Hamelberg, Edward M. Brown, Jenny J. Yang Nov 2014

Role Of Ca2+ And L-Phe In Regulating Functional Cooperativity Of Disease- Associated ‘‘Toggle’’ Calcium-Sensing Receptor Mutations, Chen Zhang, Nagaraju Mulpuri, Fadil M. Hannan, M. Andrew Nesbit, Rajesh V. Thakker, Donald Hamelberg, Edward M. Brown, Jenny J. Yang

Chemistry Faculty Publications

The Ca2+-sensing receptor (CaSR) regulates Ca2+ homeostasis in the body by monitoring extracellular levels of Ca2+ ([Ca2+]o) and amino acids. Mutations at the hinge region of the N-terminal Venus flytrap domain (VFTD) produce either receptor inactivation (L173P, P221Q) or activation (L173F, P221L) related to hypercalcemic or hypocalcemic disorders. In this paper, we report that both L173P and P221Q markedly impair the functional positive cooperativity of the CaSR as reflected by [Ca2+]o–induced [Ca2+]i oscillations, inositol-1-phosphate (IP1) accumulation and extracellular signal-regulated kinases (ERK1/2) activity. In contrast, L173F and P221L show enhanced responsiveness of these three functional readouts to [Ca2+]o. Further analysis of …

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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 Oct 2014

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 …

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A Novel Approach Using Electrospray Ionization Mass Spectrometry To Study Competitive Binding Of Small Molecules With Mixed Dna Sequences, Sarah R. Laughlin, Siming Wang, Arvind Kumar, David Boykin, W. David Wilson Oct 2014

A Novel Approach Using Electrospray Ionization Mass Spectrometry To Study Competitive Binding Of Small Molecules With Mixed Dna Sequences, Sarah R. Laughlin, Siming Wang, Arvind Kumar, David Boykin, W. David Wilson

Chemistry Faculty Publications

Minor groove binding compounds have been shown to induce changes in global DNA conformation, allosterically inhibiting DNA-protein interactions necessary for transcriptional processes. Many minor groove binders are specific for AT-base pairs but have little preference over alternating AT or A-tract sequences. Few compounds, other than polyamides, show selectivity for mixed sequences with AT and GC base pairs. Electrospray ionization mass spectrometry (ESI-MS) can provide insight on the stoichiometry and relative affinities in minor groove recognition of different DNA sequences with a library of minor groove binders. A goal in our current research is to develop new compounds that recognize mixed …

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Prostate Cancer Metastatic To Bone Has Higher Expression Of The Calcium-Sensing Receptor (Casr) Than Primary Prostate Cancer, Jie Feng, Xiaojun Xu, Bo Li, Edward Brown, Alton B. Farris, Shi-Yong Sun, Jenny J. Yang Sep 2014

Prostate Cancer Metastatic To Bone Has Higher Expression Of The Calcium-Sensing Receptor (Casr) Than Primary Prostate Cancer, Jie Feng, Xiaojun Xu, Bo Li, Edward Brown, Alton B. Farris, Shi-Yong Sun, Jenny J. Yang

Chemistry Faculty Publications

The calcium-sensing receptor (CaSR) is the principal regulator of the secretion of parathyroid hormone and plays key roles in extracellular calcium (Ca2+o) homeostasis. It is also thought to participate in the development of cancer, especially bony metastases of breast and prostate cancer. However, the expression of CaSR has not been systematically analyzed in prostate cancer from patients with or without bony metastases. By comparing human prostate cancer tissue sections in microarrays, we found that the CaSR was expressed in both normal prostate and primary prostate cancer as assessed by immunohistochemistry (IHC). We used two methods to analyze the expression level …

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Iron(Ii)-Catalyzed Intermolecular Amino-Oxygenation Of Olefins Through The N−O Bond Cleavage Of Functionalized Hydroxylamines, Deng-Fu Lu, Cheng-Liang Zhu, Zhen-Xin Jia, Hao Xu Aug 2014

Iron(Ii)-Catalyzed Intermolecular Amino-Oxygenation Of Olefins Through The N−O Bond Cleavage Of Functionalized Hydroxylamines, Deng-Fu Lu, Cheng-Liang Zhu, Zhen-Xin Jia, Hao Xu

Chemistry Faculty Publications

An iron-catalyzed diastereoselective intermolecular olefin amino-oxygenation reaction is reported, which proceeds via an iron-nitrenoid generated by the N− O bond cleavage of a functionalized hydroxylamine. In this reaction, a bench-stable hydroxylamine derivative is used as the amination reagent and oxidant. This method tolerates a range of synthetically valuable substrates that have been all incompatible with existing amino-oxygenation methods. It can also provide amino alcohol derivatives with regio- and stereochemical arrays complementary to known amino-oxygenation methods.

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Mechanistic Heterogeneity In Site Recognition By The Structurally Homologous Dna-Binding Domains Of The Ets-Family Transcription Factors Ets-1 And Pu.1, Shuo Wang, Miles H. Linde, Manoj Munde, Victor W. Carvalho, W. David Wilson, Gregory M. K. Poon Jun 2014

Mechanistic Heterogeneity In Site Recognition By The Structurally Homologous Dna-Binding Domains Of The Ets-Family Transcription Factors Ets-1 And Pu.1, Shuo Wang, Miles H. Linde, Manoj Munde, Victor W. Carvalho, W. David Wilson, Gregory M. K. Poon

Chemistry Faculty Publications

ETS-family transcription factors regulate diverse genes through binding at cognate DNA sites that overlap substantially in sequence. The DNA-binding domains of ETS proteins (ETS domains) are highly conserved structurally, yet share limited amino acid homology. To define the mechanistic implications of sequence diversity within the ETS family, we characterized the thermodynamics and kinetics of DNA site recognition by the ETS domains of Ets-1 and PU.1, which represent the extremes in amino acid divergence among ETS proteins. Even though the two ETS domains bind their optimal sites with similar affinities under physiologic conditions, their nature of site recognition differs strikingly in …

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Prototype Nerve-Specific Near-Infrared Fluorophores, Min Ho Park, Hoon Hyun, Yoshitomo Ashitate, Hideyuki Wada, Gwangli Park, Jeong Heon Lee, Costyl Njiojob, Maged Henary, John V. Frangioni, Hak Soo Choi Jun 2014

Prototype Nerve-Specific Near-Infrared Fluorophores, Min Ho Park, Hoon Hyun, Yoshitomo Ashitate, Hideyuki Wada, Gwangli Park, Jeong Heon Lee, Costyl Njiojob, Maged Henary, John V. Frangioni, Hak Soo Choi

Chemistry Faculty Publications

Nerve preservation is an important issue during most surgery because accidental transection or injury results in significant morbidity, including numbness, pain, weakness, or paralysis. Currently, nerves are still identified only by gross appearance and anatomical location during surgery, without intraoperative image guidance. Near-infrared (NIR) fluorescent light, in the wavelength range of 650-900 nm, has the potential to provide high-resolution, high-sensitivity, and real-time avoidance of nerve damage, but only if nerve-specific NIR fluorophores can be developed. In this study, we evaluated a series of Oxazine derivatives to highlight various peripheral nerve structures in small and large animals. Among the targeted fluorophores, …

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Effect Of Ca2+ On The Steady-State And Time-Resolved Emission Properties Of The Genetically Encoded Fluorescent Sensor Catcher, You Zhou, Kyril M. Solntsev, Florence Reddish, Shen Tang, Jenny J. Yang May 2014

Effect Of Ca2+ On The Steady-State And Time-Resolved Emission Properties Of The Genetically Encoded Fluorescent Sensor Catcher, You Zhou, Kyril M. Solntsev, Florence Reddish, Shen Tang, Jenny J. Yang

Chemistry Faculty Publications

We previously designed a calcium sensor CatchER (a GFP-based Calcium sensor for detecting high concentrations in the high calcium concentration environment such as ER) with a capability for monitoring calcium ion responses in various types of cells. Calcium binding to CatchER induces the ratiometric changes in the absorption spectra, as well as an increase in fluorescence emission at 510 nm upon excitation at both 395 and 488 nm. Here, we have applied the combination of the steady-state and time-resolved optical methods and Hydrogen/Deuterium isotope exchange to understand the origin of such calcium-induced optical property changes of CatchER. We first demonstrated …

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Simultaneous Mapping Of Pan And Sentinel Lymph Nodes For Real-Time Image-Guided Surgery, Yoshitomo Ashitate, Hoon Hyun, Soon Hee Kim, Jeong Heon Lee, Maged Henary, John V. Frangioni, Hak Soo Choi Apr 2014

Simultaneous Mapping Of Pan And Sentinel Lymph Nodes For Real-Time Image-Guided Surgery, Yoshitomo Ashitate, Hoon Hyun, Soon Hee Kim, Jeong Heon Lee, Maged Henary, John V. Frangioni, Hak Soo Choi

Chemistry Faculty Publications

The resection of regional lymph nodes in the basin of a primary tumor is of paramount importance in surgical oncology. Although sentinel lymph node mapping is now the standard of care in breast cancer and melanoma, over 20% of patients require a completion lymphadenectomy. Yet, there is currently no technology available that can image all lymph nodes in the body in real time, or assess both the sentinel node and all nodes simultaneously. In this study, we report an optical fluorescence technology that is capable of simultaneous mapping of pan lymph nodes (PLNs) and sentinel lymph nodes (SLNs) in the …

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Structures Of Darunavir-Resistant Hiv‑1 Protease Mutant Reveal Atypical Binding Of Darunavir To Wide Open Flaps, Ying Zhang, Yu-Chung E. Chang, John M. Louis, Yuan Fang Wang, Robert W. Harrison, Irene Weber Apr 2014

Structures Of Darunavir-Resistant Hiv‑1 Protease Mutant Reveal Atypical Binding Of Darunavir To Wide Open Flaps, Ying Zhang, Yu-Chung E. Chang, John M. Louis, Yuan Fang Wang, Robert W. Harrison, Irene Weber

Chemistry Faculty Publications

The molecular basis for high resistance to clinical inhibitors of HIV-1 protease (PR) was examined for the variant designated PRP51 that was selected for resistance to darunavir (DRV). High resolution crystal structures of PRP51 with the active site D25N mutation revealed a ligand-free form and an inhibitor-bound form showing a unique binding site and orientation for DRV. This inactivating mutation is known to increase the dimer dissociation constant and decrease DRV affinity of PR. The PRP51‑D25N dimers were in the open conformation with widely separated flaps, as reported for other highly resistant variants. PRP51‑D25N dimer bound two DRV molecules and …

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Nonproteolytic Roles Of 19s Atpases In Transcription Of Ciitapiv Genes, Nagini Maganti, Tomika Moody, Agnieszka D. Truax, Meghna Thakkar, Alexander M. Spring, Markus W. Germann, Susanna F. Greer Mar 2014

Nonproteolytic Roles Of 19s Atpases In Transcription Of Ciitapiv Genes, Nagini Maganti, Tomika Moody, Agnieszka D. Truax, Meghna Thakkar, Alexander M. Spring, Markus W. Germann, Susanna F. Greer

Chemistry Faculty Publications

Accumulating evidence shows the 26S proteasome is involved in the regulation of gene expression. We and others have demonstrated that proteasome components bind to sites of gene transcription, regulate covalent modifications to histones, and are involved in the assembly of activator complexes in mammalian cells. The mechanisms by which the proteasome influences transcription remain unclear, although prior observations suggest both proteolytic and non-proteolytic activities. Here, we define novel, non-proteolytic, roles for each of the three 19S heterodimers, represented by the 19S ATPases Sug1, S7, and S6a, in mammalian gene expression using the inflammatory gene CIITApIV. These 19S ATPases are recruited …

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Kinetics And Structures On The Molecular Path To The Quadruplex Form Of The Human Telomere, W. David Wilson, Ananya Paul Feb 2014

Kinetics And Structures On The Molecular Path To The Quadruplex Form Of The Human Telomere, W. David Wilson, Ananya Paul

Chemistry Faculty Publications

No abstract provided.

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The Unusual Monomer Recognition Of Guanine-Containing Mixed Sequence Dna By A Dithiophene Heterocyclic Diamidine, Manoj Munde, Arvind Kumar, Paul Peixoto, Sabine Depauw, Mohamed A. Ismail, Abdelbasset A. Farahat, Ananya Paul, Martial V. Say, Marie-HéLèNe David-Cordonnier, David Boykin, W. David Wilson Feb 2014

The Unusual Monomer Recognition Of Guanine-Containing Mixed Sequence Dna By A Dithiophene Heterocyclic Diamidine, Manoj Munde, Arvind Kumar, Paul Peixoto, Sabine Depauw, Mohamed A. Ismail, Abdelbasset A. Farahat, Ananya Paul, Martial V. Say, Marie-HéLèNe David-Cordonnier, David Boykin, W. David Wilson

Chemistry Faculty Publications

DB1255 is a symmetrical diamidinophenyl-dithiophene that exhibits cellular activity by binding to DNA and inhibiting binding of ERG, an ETS family transcription factor that is commonly overexpressed or translocated in leukemia and prostate cancer [Nhili, R., Peixoto, P., Depauw, S., Flajollet, S., Dezitter, X., Munde, M. M., Ismail, M. A., Kumar, A., Farahat, A. A., Stephens, C. E., Duterque-Coquillaud, M., Wilson, W. D., Boykin, D. W., and David-Cordonnier, M. H. (2013) Nucleic Acids Res. 41, 125−138]. Because transcription factor inhibition is complex but is an attractive area for anticancer and antiparasitic drug development, we have evaluated the DNA interactions of …

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The Unusual Monomer Recognition Of Guanine-Containing Mixed Sequence Dna By A Dithiophene Heterocyclic Diamidine, Manoj Munde, Arvind Kumar, Paul Peixoto, Sabine Depauw, Mohamed A. Ismail, Abdelbasset A. Farahat, Ananya Paul, Martial V. Say, Marie-HéLèNe David-Cordonnier, David Boykin, W. David Wilson Feb 2014

The Unusual Monomer Recognition Of Guanine-Containing Mixed Sequence Dna By A Dithiophene Heterocyclic Diamidine, Manoj Munde, Arvind Kumar, Paul Peixoto, Sabine Depauw, Mohamed A. Ismail, Abdelbasset A. Farahat, Ananya Paul, Martial V. Say, Marie-HéLèNe David-Cordonnier, David Boykin, W. David Wilson

Chemistry Faculty Publications

DB1255 is a symmetrical diamidinophenyl-dithiophene that exhibits cellular activity by binding to DNA and inhibiting binding of ERG, an ETS family transcription factor that is commonly overexpressed or translocated in leukemia and prostate cancer [Nhili, R., Peixoto, P., Depauw, S., Flajollet, S., Dezitter, X., Munde, M. M., Ismail, M. A., Kumar, A., Farahat, A. A., Stephens, C. E., Duterque-Coquillaud, M., Wilson, W. D., Boykin, D. W., and David-Cordonnier, M. H. (2013) Nucleic Acids Res. 41, 125−138]. Because transcription factor inhibition is complex but is an attractive area for anticancer and antiparasitic drug development, we have evaluated the DNA interactions of …

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Dna Binding Polyamides And The Importance Of Dna Recognition In Their Use As Gene-Specific And Antiviral Agents, Kevin J. Koeller, G Davis Harris, Karl Aston, Gaofei He, Carlos H. Castaneda, Melissa A. Thornton, Terri G. Edwards, Shuo Wang, Rupesh Nanjunda, W. David Wilson, Chris Fisher, James K. Bashkin Feb 2014

Dna Binding Polyamides And The Importance Of Dna Recognition In Their Use As Gene-Specific And Antiviral Agents, Kevin J. Koeller, G Davis Harris, Karl Aston, Gaofei He, Carlos H. Castaneda, Melissa A. Thornton, Terri G. Edwards, Shuo Wang, Rupesh Nanjunda, W. David Wilson, Chris Fisher, James K. Bashkin

Chemistry Faculty Publications

There is a long history for the bioorganic and biomedical use of N-methyl-pyrrole-derived polyamides (PAs) that are higher homologs of natural products such as distamycin A and netropsin. This work has been pursued by many groups, with the Dervan and Sugiyama groups responsible for many breakthroughs. We have studied PAs since about 1999, partly in industry and partly in academia. Early in this program, we reported methods to control cellular uptake of polyamides in cancer cell lines and other cells likely to have multidrug resistance efflux pumps induced. We went on to discover antiviral polyamides active against HPV31, where SAR …

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Novel Complex Mad Phasing And Rnase H Structural Insights Using Selenium Oligonucleotides, Zhen Huang, Rob Abdur, Oksana Gerlits, Jianhua Gan, Jozef Salon, Andrey Y. Kovalevsky, Alexander A. Chumanevich, Irene Weber Jan 2014

Novel Complex Mad Phasing And Rnase H Structural Insights Using Selenium Oligonucleotides, Zhen Huang, Rob Abdur, Oksana Gerlits, Jianhua Gan, Jozef Salon, Andrey Y. Kovalevsky, Alexander A. Chumanevich, Irene Weber

Chemistry Faculty Publications

No abstract provided.

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Glycan Based Detection And Drug Susceptibility Of Influenza Virus, Hieu Dinh, Xiaohu Zhang, Joyce Sweeney, Yang Yang, Yun He, Abasaheb Dhawane, Suri S. Iyer Jan 2014

Glycan Based Detection And Drug Susceptibility Of Influenza Virus, Hieu Dinh, Xiaohu Zhang, Joyce Sweeney, Yang Yang, Yun He, Abasaheb Dhawane, Suri S. Iyer

Chemistry Faculty Publications

ABSTRACT: We have developed a panel of synthetic glycans as receptor mimics for the specific capture of influenza viruses. The glycans were printed onto commercial glass slides using a free amine at the end of a spacer to generate a small focused microarray. The microarray was evaluated for its ability to capture three different strains of influenza A virus, two H1N1, A/Brisbane/59/2007 and A/Solomon Islands/3/2006 and one H3N2, A/Aichi/2/1968. We observed an excellent detection ability with some compounds exhibiting clinically relevant (101 plaque forming units) limit of detection. We also tested the drug susceptibility of current antivirals, Zanamivir and Ostelamivir …

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Myoplasmic Resting Ca2+ Regulation By Ryanodine Receptors Is Under The Control Of A Novel Ca2+-Binding Region Of The Receptor, Yanyi Chen, Shenghui Xue, Juan Zou, Jose Lopez, Jenny J. Yang, Claudio Perez Jan 2014

Myoplasmic Resting Ca2+ Regulation By Ryanodine Receptors Is Under The Control Of A Novel Ca2+-Binding Region Of The Receptor, Yanyi Chen, Shenghui Xue, Juan Zou, Jose Lopez, Jenny J. Yang, Claudio Perez

Chemistry Faculty Publications

Passive SR (sarcoplasmic reticulum) Ca2+ leak through the RyR (ryanodine receptor) plays a critical role in the mechanisms that regulate [Ca2+ ]rest (intracellular resting myoplasmic free Ca2+ concentration) in muscle. This process appears to be isoform-specific as expression of either RyR1 or RyR3 confers on myotubes different [Ca2+ ]rest. Using chimaeric RyR3–RyR1 receptors expressed in dyspedic myotubes, we show that isoformdependent regulation of [Ca2+ ]rest is primarily defined by a small region of the receptor encompassing amino acids 3770– 4007 of RyR1 (amino acids 3620–3859 of RyR3) named as the CLR (Ca2+ leak regulatory) region. [Ca2+ ]rest regulation by the …

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Identification Of An L-Phenylalanine Binding Site Enhancing The Cooperative Responses Of The Calcium Sensing Receptor To Calcium, Chen Zhang, Yun Huang, Yusheng Jiang, Nagaraju Mulpuri, Ling Wei, Donald Hamelberg, Edward M. Brown, Jenny J. Yang Jan 2014

Identification Of An L-Phenylalanine Binding Site Enhancing The Cooperative Responses Of The Calcium Sensing Receptor To Calcium, Chen Zhang, Yun Huang, Yusheng Jiang, Nagaraju Mulpuri, Ling Wei, Donald Hamelberg, Edward M. Brown, Jenny J. Yang

Chemistry Faculty Publications

Functional positive cooperative activation of the extracellular calcium ([Ca2+]o)-sensing receptor (CaSR), a member of the family C G protein-coupled receptors (GPCRs), by [Ca2+]o or amino acids elicits intracellular Ca2+ ([Ca2+]i) oscillations. Here, we report the central role of predicted Ca2+-binding Site 1 within the hinge region of the extracellular domain (ECD) of CaSR and its interaction with other Ca2+-binding sites within the ECD in tuning functional positive homotropic cooperativity caused by changes in [Ca2+]o. Next, we identify an adjacent L-Phe-binding pocket that is responsible for positive heterotropic cooperativity between [Ca2+]o and L- Phe in eliciting CaSR-mediated [Ca2+]i oscillations. The hetero-communication …

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Design And Synthesis Of Heterocyclic Cations For Specific Dna Recognition: From At-Rich To Mixed-Base-Pair Dna Sequences, Yun Chai, Ananya Paul, Michael Rettig, W. David Wilson, David Boykin Jan 2014

Design And Synthesis Of Heterocyclic Cations For Specific Dna Recognition: From At-Rich To Mixed-Base-Pair Dna Sequences, Yun Chai, Ananya Paul, Michael Rettig, W. David Wilson, David Boykin

Chemistry Faculty Publications

The compounds synthesized in this research were designed with the goal of establishing a new paradigm for mixed-base-pair DNA sequence-specific recognition. The design scheme starts with a cell-permeable heterocyclic cation that binds to AT base pair sites in the DNA minor groove. Modifications were introduced in the original compound to include an Hbond accepting group to specifically recognize the G-NH that projects into the minor groove. Therefore, a series of heterocyclic cations substituted with an azabenzimidazole ring has been designed and synthesized for mixed-base-pair DNA recognition. The most successful compound, 12a, had an azabenzimidazole to recognize G and additional modifications …

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Spectrophotometric And Spectrofluorimetric Studies On Azilsartan Medoxomil And Chlorthalidone To Be Utilized In Their Determination In Pharmaceuticals, Walid M. Ebeid, Ehab F. Elkady, Asmaa A. El-Zaher, Ramzia I. El-Bagary, Gabor Patonay Jan 2014

Spectrophotometric And Spectrofluorimetric Studies On Azilsartan Medoxomil And Chlorthalidone To Be Utilized In Their Determination In Pharmaceuticals, Walid M. Ebeid, Ehab F. Elkady, Asmaa A. El-Zaher, Ramzia I. El-Bagary, Gabor Patonay

Chemistry Faculty Publications

The recently approved angiotensin II receptor blocker, azilsartan medoxomil (AZL), was determined spectrophotometrically and spectrofluorimetrically in its combination with chlorthalidone (CLT) in their combined dosage form. The UV-spectrophotometric technique depends on simultaneous measurement of the first derivative spectra for AZL and CLT at 286 and 257 nm, respectively, in methanol. The spectrofluorimetric technique depends on measurement of the fourth derivative of the synchronous spectra intensities of AZL in presence of CLT at 298 nm in methanol. The effects of different solvents on spectrophotometric and spectrofluorimetric responses were studied. For, the spectrofluorimetric study, the effect of pH and micelle-assisted fluorescence enhancement …

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