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- Amino acid (2)
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- G protein-coupled receptors (GPCR) (2)
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- NMR (2)
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- Spectroscopy (2)
- 2-selenouridine triphosphate; RNA transcription; RNA structure and function; hammerhead ribozyme; RNA crystallography (1)
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- Calcium-sensing receptor; prostate; cancer; bone; metastasis (1)
- Calcium; Calcium binding proteins; Drug discovery; G protein coupled receptors (GPCR); Glutamate receptors metabotropic; allosteric modulators; orthosteric agonist; orthosteric antagonist (1)
- Capillary zone electrophoresis (1)
- Cell cycle (1)
- Cervical cancer. (1)
- Chemistry (1)
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- Competition; mass spectrometry; electrospray; minor groove binder; DNA; transcription factor; specificity (1)
- Completion lymphadenectomy (1)
- Contrast agents (1)
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- Cyanine Dyes (1)
- Cyanine dye; unsymmetrical; synthesis; optical properties; DFT calculations; DNA grooves (1)
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Articles 1 - 30 of 46
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Benz[C,D]Indolium-Containing Monomethine Cyanine Dyes: Synthesis And Photophysical Properties, Eduardo Soriano, Cory Holder, Andrew R. Levitz, Maged Henary
Benz[C,D]Indolium-Containing Monomethine Cyanine Dyes: Synthesis And Photophysical Properties, Eduardo Soriano, Cory Holder, Andrew R. Levitz, Maged Henary
Chemistry Faculty Publications
Asymmetric monomethine cyanines have been extensively used as probes for nucleic acids among other biological systems. Herein we report the synthesis of seven monomethine cyanine dyes that have been successfully prepared with various heterocyclic moieties such as quinoline, benzoxazole, benzothiazole, dimethyl indole, and benz[e]indole adjoining benz[c,d]indol-1-ium, which was found to directly influence their optical and energy profiles. In this study the optical properties vs. structural changes were investigated using nuclear magnetic resonance and computational approaches. The twisted conformation unique to monomethine cyanines was exploited in DNA binding studies where the newly designed sensor displayed an increase in fluorescence when bound …
Stochastic Optical Reconstruction Microscopy Imaging Of Microtubule Arrays In Intact Arabidopsis Thaliana Seedling Roots, Bin Dong, Xiaochen Yang, Shaobin Zhu, Diane C. Bassham, Ning Fang
Stochastic Optical Reconstruction Microscopy Imaging Of Microtubule Arrays In Intact Arabidopsis Thaliana Seedling Roots, Bin Dong, Xiaochen Yang, Shaobin Zhu, Diane C. Bassham, Ning Fang
Chemistry Faculty Publications
Super-resolution fluorescence microscopy has generated tremendous success in revealing detailed subcellular structures in animal cells. However, its application to plant cell biology remains extremely limited due to numerous technical challenges, including the generally high fluorescence background of plant cells and the presence of the cell wall. In the current study, stochastic optical reconstruction microscopy (STORM) imaging of intact Arabidopsis thaliana seedling roots with a spatial resolution of 20–40 nm was demonstrated. Using the super-resolution images, the spatial organization of cortical microtubules in different parts of a whole Arabidopsis root tip was analyzed quantitatively, and the results show the dramatic differences …
O-Glcnacylation Of G6pd Promotes The Pentose Phosphate Pathway And Tumor Growth, Xiongjian Rao, Xiaotao Duan, Weimin Mao, Xuexia Li, Zhonghua Li, Qian Li, Zhiguo Zheng, Haimiao Xu, Min Chen, Peng George Wang, Yingjie Wang, Binghui Shen, Wen Yi
O-Glcnacylation Of G6pd Promotes The Pentose Phosphate Pathway And Tumor Growth, Xiongjian Rao, Xiaotao Duan, Weimin Mao, Xuexia Li, Zhonghua Li, Qian Li, Zhiguo Zheng, Haimiao Xu, Min Chen, Peng George Wang, Yingjie Wang, Binghui Shen, Wen Yi
Chemistry Faculty Publications
The pentose phosphate pathway (PPP) plays a critical role in macromolecule biosynthesis and maintaining cellular redox homoeostasis in rapidly proliferating cells. Upregulation of the PPP has been shown in several types of cancer. However, how the PPP is regulated to confer a selective growth advantage on cancer cells is not well understood. Here we show that glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, is dynamically modified with an O-linked b-N-acetylglucosamine sugar in response to hypoxia. Glycosylation activates G6PD activity and increases glucose flux through the PPP, thereby providing precursors for nucleotide and lipid biosynthesis, and reducing equivalents for …
Hydrogen Sulfide Prodrugs—A Review, Yueqin Zheng, Xingyue Ji, Kaili Ji, Binghe Wang
Hydrogen Sulfide Prodrugs—A Review, Yueqin Zheng, Xingyue Ji, Kaili Ji, Binghe Wang
Chemistry Faculty Publications
Abstract Hydrogen sulfide (H2S) is recognized as one of three gasotransmitters together with nitric oxide (NO) and carbon monoxide (CO). As a signaling molecule, H2S plays an important role in physiology and shows great potential in pharmaceutical applications. Along this line, there is a need for the development of H2S prodrugs for various reasons. In this review, we summarize different H2S
Chemotherapy Of Second Stage Human African Trypanosomiasis: Comparison Between The Parenteral Diamidine Db829 And Its Oral Prodrug Db868 In Vervet Monkeys, John K. Thuita, Kristina K. Wolf, Grace A. Murilla, Arlene S. Bridges, David Boykin, James N. Mutuku, Qiang Liu, Susan K. Jones, Charles O. Gem, Shelley Ching, Richard R. Tidwell, Michael Z. Wang, Mary F. Paine, Reto Brun
Chemotherapy Of Second Stage Human African Trypanosomiasis: Comparison Between The Parenteral Diamidine Db829 And Its Oral Prodrug Db868 In Vervet Monkeys, John K. Thuita, Kristina K. Wolf, Grace A. Murilla, Arlene S. Bridges, David Boykin, James N. Mutuku, Qiang Liu, Susan K. Jones, Charles O. Gem, Shelley Ching, Richard R. Tidwell, Michael Z. Wang, Mary F. Paine, Reto Brun
Chemistry Faculty Publications
Human African trypanosomiasis (HAT, sleeping sickness) ranks among the most neglected tropical diseases based on limited availability of drugs that are safe and efficacious, particularly against the second stage (central nervous system [CNS]) of infection. In response to this largely unmet need for new treatments, the Consortium for Parasitic Drug Development developed novel parenteral diamidines and corresponding oral prodrugs that have shown cure of a murine model of second stage HAT. As a rationale for selection of one of these compounds for further development, the pharmacokinetics and efficacy of intramuscular (IM) active diamidine 2,5-bis(5-amidino-2-pyridyl)furan (DB829; CPD-0802) and oral prodrug2,5- bis[5-(N-methoxyamidino)-2-pyridyl]furan …
Understanding Mixed Sequence Dna Recognition By Novel Designed Compounds: The Kinetic And Thermodynamic Behavior Of Azabenzimidazole Diamidines, Ananya Paul, W. David Wilson, David Boykin, Yun Chai
Understanding Mixed Sequence Dna Recognition By Novel Designed Compounds: The Kinetic And Thermodynamic Behavior Of Azabenzimidazole Diamidines, Ananya Paul, W. David Wilson, David Boykin, Yun Chai
Chemistry Faculty Publications
Sequence-specific recognition of DNA by small organic molecules offers a potentially effective approach for the external regulation of gene expression and is an important goal in cell biochemistry. Rational design of compounds from established modules can potentially yield compounds that bind strongly and selectively with specific DNA sequences. An initial approach is to start with common A·T bp recognition molecules and build in G·C recognition units. Here we report on the DNA interaction of a synthetic compound that specifically binds to a G·C bp in the minor groove of DNA by using an azabenzimidazole moiety. The detailed interactions were evaluated …
Efficient Chemoenzymatic Synthesis Of An N-Glycan Isomer Library, Lei Li, Yunpeng Liu, Cheng Ma, Jingyao Qu, Angie D. Calderon, Baolin Wu, Na Wei, Xuan Wang, Yuxi Guo, Zhongying Xiao, Jing Song, Go Sugiarto, Yanhong Li, Hai Yu, Xi Chen, Peng George Wang
Efficient Chemoenzymatic Synthesis Of An N-Glycan Isomer Library, Lei Li, Yunpeng Liu, Cheng Ma, Jingyao Qu, Angie D. Calderon, Baolin Wu, Na Wei, Xuan Wang, Yuxi Guo, Zhongying Xiao, Jing Song, Go Sugiarto, Yanhong Li, Hai Yu, Xi Chen, Peng George Wang
Chemistry Faculty Publications
Quantification, characterization and biofunctional studies of N-glycans on proteins remain challenging tasks due to the complexity, diversity and low abundance of these glycans. The availability of structurally defined N-glycan (especially isomer) libraries is essential to help solve these tasks. We report herein an efficient chemoenzymatic strategy, namely Core Synthesis/Enzymatic Extension (CSEE), for rapid production of diverse N-glycans. Starting with 5 chemically prepared building blocks, 8 N-glycan core structures containing one or two terminal N-acetyl-D-glucosamine (GlcNAc) residue(s) were chemically synthesized via consistent use of oligosaccharyl thioethers as glycosylation donors in a convergent fragment coupling strategy. Each of these core structures was …
May The Best Molecule Win: Competition Esi Mass Spectrometry, Sarah R. Laughlin, W. David Wilson
May The Best Molecule Win: Competition Esi Mass Spectrometry, Sarah R. Laughlin, W. David Wilson
Chemistry Faculty Publications
Electrospray ionization mass spectrometry has become invaluable in the characterization of macromolecular biological systems such as nucleic acids and proteins. Recent advances in the field of mass spectrometry and the soft conditions characteristic of electrospray ionization allow for the investigation of non-covalent interactions among large biomolecules and ligands. Modulation of genetic processes through the use of small molecule inhibitors with the DNA minor groove is gaining attention as a potential therapeutic approach. In this review, we discuss the development of a competition method using electrospray ionization mass spectrometry to probe the interactions of multiple DNA sequences with libraries of minor …
Integrative Modeling Of Macromolecular Assemblies From Low To Near-Atomic Resolution, Xiaojun Xu, Chunli Yan, Robert Wohlhueter, Ivaylo Ivanov
Integrative Modeling Of Macromolecular Assemblies From Low To Near-Atomic Resolution, Xiaojun Xu, Chunli Yan, Robert Wohlhueter, Ivaylo Ivanov
Chemistry Faculty Publications
While conventional high-resolution techniques in structural biology are challenged by the size and flexibility of many biological assemblies, recent advances in low-resolution techniques such as cryo-electron microscopy (cryo-EM) and small angle X-ray scattering (SAXS) have opened up new avenues to define the structures of such assemblies. By systematically combining various sources of structural, biochemical and biophysical information, integrativemodeling approaches aimto provide a unified structural description of such assemblies, starting from high-resolution structures of the individual components and integrating all available information from low-resolution experimental methods. In this review, we describe integrative modeling approaches, which use complementary data from either cryo-EM …
Pancreas-Targeted Nir Fluorophores For Dual-Channel Image-Guided Abdominal Surgery, Hideyuki Wada, Hoon Hyun, Christina Vargas, Julien Gravier, Gwangli Park, Sylvain Gioux, John V. Frangioni, Maged Henary, Hak Soo Choi
Pancreas-Targeted Nir Fluorophores For Dual-Channel Image-Guided Abdominal Surgery, Hideyuki Wada, Hoon Hyun, Christina Vargas, Julien Gravier, Gwangli Park, Sylvain Gioux, John V. Frangioni, Maged Henary, Hak Soo Choi
Chemistry Faculty Publications
Objective: Pancreas-related complications are some of the most serious ones in abdominal surgery. The goal of this study was to develop and validate novel near-infrared (NIR) fluorophores that would enable real-time pancreas imaging to avoid the intraoperative pancreatic injury. Design: After initial screening of a large NIR fluorophore library, the performance of 3 selected pancreas-targeted 700 nm NIR fluorophores, T700-H, T700-F, and MB, were quantified in mice, rats, and pigs. Dose ranging using 25 and 100 nmol, and 2.5 μmol of T700-F, and its imaging kinetics over a 4 h period were tested in each species. Three different 800 nm …
Crystallographic And Spectroscopic Snapshots Reveal A Dehydrogenase In Action, Lu Huo, Ian Davis, Fange Liu, Babak Andi, Shingo Esaki, Hiroaki Iwaki, Yoshie Hasegawa, Allen M. Orville, Aimin Liu
Crystallographic And Spectroscopic Snapshots Reveal A Dehydrogenase In Action, Lu Huo, Ian Davis, Fange Liu, Babak Andi, Shingo Esaki, Hiroaki Iwaki, Yoshie Hasegawa, Allen M. Orville, Aimin Liu
Chemistry Faculty Publications
Aldehydes are ubiquitous intermediates in metabolic pathways and their innate reactivity can often make them quite unstable. There are several aldehydic intermediates in the metabolic pathway for tryptophan degradation that can decay into neuroactive compounds that have been associated with numerous neurological diseases. An enzyme of this pathway, 2-aminomuconate-6-semialdehyde dehydrogenase, is responsible for ‘disarming’ the final aldehydic intermediate. Here we show the crystal structures of a bacterial analogue enzyme in five catalytically relevant forms: resting state, one binary and two ternary complexes, and a covalent, thioacyl intermediate. We also report the crystal structures of a tetrahedral, thiohemiacetal intermediate, a thioacyl …
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
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 …
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
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 …
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
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 …
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
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 …
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
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.
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
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 …
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
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, …
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
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 …
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
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 …
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
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 …
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
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 …
Kinetics And Structures On The Molecular Path To The Quadruplex Form Of The Human Telomere, W. David Wilson, Ananya Paul
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.
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
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 …
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
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 …
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
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 …
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
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.
Glycan Based Detection And Drug Susceptibility Of Influenza Virus, Hieu Dinh, Xiaohu Zhang, Joyce Sweeney, Yang Yang, Yun He, Abasaheb Dhawane, Suri S. Iyer
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 …
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
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 …
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
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 …