Physical Sciences and Mathematics | Open Access Articles

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 …

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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 …

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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 …

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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

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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 …

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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 …

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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 …

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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 …

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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 …

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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 …

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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 …

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Full-Text Articles in Physical Sciences and Mathematics

Benz[C,D]Indolium-Containing Monomethine Cyanine Dyes: Synthesis And Photophysical Properties, Eduardo Soriano, Cory Holder, Andrew R. Levitz, Maged Henary

Chemistry Faculty Publications

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

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

Hydrogen Sulfide Prodrugs—A Review, Yueqin Zheng, Xingyue Ji, Kaili Ji, Binghe Wang

Chemistry Faculty Publications

Chemistry Faculty Publications

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

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

May The Best Molecule Win: Competition Esi Mass Spectrometry, Sarah R. Laughlin, W. David Wilson

Chemistry Faculty Publications

Integrative Modeling Of Macromolecular Assemblies From Low To Near-Atomic Resolution, Xiaojun Xu, Chunli Yan, Robert Wohlhueter, Ivaylo Ivanov

Chemistry Faculty Publications

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

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