Biotechnological Production Of 1,2,4-Butanetriol: An Efficient Process To Synthesize Energetic Material Precursor From Renewable Biomass, 2015 Chinese Academy of Sciences
Biotechnological Production Of 1,2,4-Butanetriol: An Efficient Process To Synthesize Energetic Material Precursor From Renewable Biomass, Yujin Cao, Wei Niu, Jiantao Guo, Mo Xian, Huizhou Liu
Faculty Publications -- Chemistry Department
1,2,4-Butanetriol (BT) is a valuable chemical with extensive applications in many different fields. The traditional chemical routes to synthesize BT suffer from many drawbacks, e.g., harsh reaction conditions, multiple steps and poor selectivity, limiting its industrial production. In this study, an engineered Escherichia coli strain was constructed to produce BT from xylose, which is a major component of the lignocellulosic biomass. Through the coexpression of a xylose dehydrogenase (CCxylB) and a xylonolactonase (xylC) from Caulobacter crescentus, native E. coli xylonate dehydratase (yjhG), a 2-keto acid decarboxylase from Pseudomonas putida (mdlC) and native E. coli aldehyde reductase (adhP ...
New Insight Into The Helium-Induced Damage In Max Phase Ti3Alc2 By First-Principles Studies, 2015 Division of Functional Materials and Nanodevices, Ningbo Institute of Materials Technology and Engineering, Chinese Academy of Sciences, Ningbo, Zhejiang
New Insight Into The Helium-Induced Damage In Max Phase Ti3Alc2 By First-Principles Studies, Yiguo Xu, Xiaojing Bai, Xianhu Zha, Qing Huang, Jian He, Kan Luo, Yuhong Zhou, Timothy C. Germann, Joseph S. Francisco, Shiyu Du
Faculty Publications -- Chemistry Department
In the present work, the behavior of He in the MAX phase Ti3AlC2 material is investigated using first-principle methods. It is found that, according to the predicted formation energies, a single He atom favors residing near the Al plane in Ti3AlC2. The results also show that Al vacancies are better able to trap He atoms than either Ti or C vacancies. The formation energies for the secondary vacancy defects near an Al vacancy or a C vacancy are strongly influenced by He impurity content. According to the present results, the existence of trapped He atoms in primary Al vacancy can ...
Energetics, Structure, And Rovibrational Spectroscopic Properties Of The Sulfurous Anions Sno− And Osn−, 2015 Georgia Southern University
Energetics, Structure, And Rovibrational Spectroscopic Properties Of The Sulfurous Anions Sno− And Osn−, Ryan C. Fortenberry, Joseph S. Francisco
Faculty Publications -- Chemistry Department
The SNO− and OSN− anions are shown in this work to be very stable negatively charged species in line with other recent work [T. Trabelsi et al., J. Chem. Phys. 143, 164301 (2015)]. Utilizing established quartic force field techniques, the structural and rovibrational data for these anions are produced. The SNO− anion is less linear and has weaker bonds than the corresponding neutral radical giving much smaller rotational constants.OSN− is largely unchanged in these regards with inclusion of the additional electron.The S–N bond is actually stronger,and the rotational constants of OSN− versus OSN are similar. The ...
Total Synthesis Of Biologically Active Natural And Unnatural Products, 2015 Georgia Southern University
Total Synthesis Of Biologically Active Natural And Unnatural Products, Julia Heimberger
Electronic Theses and Dissertations
Herbarin A and B were isolated from the fungal strains of Cladosporium herbarum found in marine sponges Aplysina aerophoba and Callyspongia aerizusa. Total synthesis of Herbarin A and B was achieved by carrying out a multi-step synthesis approach, and the antioxidant properties were evaluated using FRAP assay. Toxicity of these compounds was determined using a zebrafish embryo model. Furthermore, synthesis of C-6 alkyl-azaarene derivatives of nucleosides by Csp3-H bond functionalization were investigated. Effective incorporation of 2-methylazaarene moiety at the C-6 position of the protected inosine nucleoside provided a new class of compounds with anticipated enhanced biological activity.
Stereocontrolled 1,2-Cis Glycosylation As The Driving Force Of Progress In Synthetic Carbohydrate Chemistry, 2014 University of Missouri–St. Louis
Stereocontrolled 1,2-Cis Glycosylation As The Driving Force Of Progress In Synthetic Carbohydrate Chemistry, Swati S. Nigudkar, Alexei V. Demchenko
Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), 2014 Dow Europe GmbH
Can Acute Dermal Systemic Toxicity Tests Be Replaced With Oral Tests? A Comparison Of Route-Specific Systemic Toxicity And Hazard Classifications Under The Globally Harmonized System Of Classification And Labelling Of Chemicals (Ghs), Nigel P. Moore, David J. Andrew, Donald L. Bjerke, Stuart Creton, David Dreher, Thomas Holmes, Pilar Prieto, Troy Seidle, Tim G. Rowan
Troy Seidle, PhD
Acute systemic toxicity data (LD50 values) and hazard classifications derived in the rat following oral administration and dermal application have been analysed to examine whether or not orally-derived hazard classification or LD50 values can be used to determine dermal hazard classification. Comparing the oral and dermal classifications for 335 substances derived from oral and dermal LD50 values respectively revealed 17% concordance, and indicated that 7% of substances would be classified less severely while 76% would be classified more severely if oral classifications were applied directly to the dermal route. In contrast, applying the oral LD50 values within the dermal classification ...
The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, 2014 European Centre for the Validation of Alternative Methods
The Development Of New Concepts For Assessing Reproductive Toxicity Applicable To Large Scale Toxicological Programmes, S. Bremer, C. Pellizzer, S. Hoffmann, T. Seidle, T. Hartung
Troy Seidle, PhD
Large scale toxicological testing programmes which are currently ongoing such as the new European chemical legislation REACH require the development of new integrated testing strategies rather than applying traditional testing schemes to thousands of chemicals. The current practice of requiring in vivo testing for every possible adverse effect endanger the success of these programmes due (i) to limited testing facilities and sufficient capacity of scientific/technical knowledge for reproductive toxicity; (ii) an unacceptable number of laboratory animals involved (iii) an intolerable number of chemicals classified as false positive.
A key aspect of the implementation of new testing strategies is the ...
Colloidal And Biological Properties Of Triscationic Amphiphiles With One Or Two Tails, 2014 James Madison University
Colloidal And Biological Properties Of Triscationic Amphiphiles With One Or Two Tails, John N. Marafino
The decline in the development of novel antimicrobials, combined with the misusage and over prescription of antibiotics, has contributed to the increasing prevalence of antimicrobial-resistant infections. Thus development of effective novel disinfectants could reduce the transmission of pathogens and decrease the risk of infection by antibiotic resistant organisms. The antimicrobial activity of amphiphiles, compounds with hydrophobic and hydrophilic regions, was first reported in 1935, and has influenced the synthesis of amphiphiles with variations in structure. In this study, three series of amphiphiles were synthesized by two subsequent Menshutkin reactions. Each amphiphile contains one or two hydrocarbon tails ranging from 8 ...
New 4-Aminoquinoline Compounds To Reverse Drug Resistance In P. Falciparum Malaria, And A Survey Of Early European Antimalarial Treatments, Katherine May Liebman
Dissertations and Theses
Intermittent fevers caused by Plasmodium parasites have been known for millennia, and have caused untold human suffering. Today, millions of people are afflicted by malaria each year, and hundreds of thousands die. Historically, the most successful synthetic antimalarial drug was chloroquine, as it was safe, inexpensive, and highly efficacious. However, plasmodial resistance to chloroquine now greatly limits its utility. Previously in our laboratories it has been shown that attachment of a "reversal agent moiety" to the side chain of chloroquine can result in the restoration of activity against chloroquine-resistant strains of P. falciparum malaria. In the first part of the ...
Reaction Rates Of Amino Acids With Derivatives Of The Anticancer Drug Cisplatin, 2014 Western Kentucky University
Reaction Rates Of Amino Acids With Derivatives Of The Anticancer Drug Cisplatin, Celia Jess Whelan
Honors College Capstone Experience/Thesis Projects
We are studying reactions of cisplatin derivatives, which differ in both size and shape, with various amino acids. When reaction with DNA occurs, apoptosis is observed, ideally leading to termination of the cancer. Due to the affinity of cisplatin for sulfur-containing amino acids, reaction with proteins may occur prior to access to the DNA, producing a large array of products, which could potentially be toxic to the human body. Both the size and shape of the platinum complexes often affect the reactions with protein targets more so than with DNA targets. By performing reactions of specific amino acids targets with ...
Ultrafast Interfacial Electron Transfer Across Molecule-Tio2 Nanocomposites: Towards Solar Cells And Two Photon Absorption, 2014 Western Michigan University
Ultrafast Interfacial Electron Transfer Across Molecule-Tio2 Nanocomposites: Towards Solar Cells And Two Photon Absorption, Edwin Mghanga
Interfacial charge transfer (ICT) across the molecule-TiO2 nanoparticle interface has gained enormous research attention for applications in dye sensitized solar cells (DSSC), photo-catalysis, water splitting and nonlinear optics. DSSCs are promising clean alternative energy sources. However, current DSSCs suffer from lower efficiencies and higher cost. Better understanding of the ICT processes in DSSCs can help solve these problems. We have used two strategies to understand ICT in the context of DSSCs. Firstly, we used a computationally validated anchor group, acetylacetonate (acac) to bind molecules to the semiconductor surface and facilitate charge separation. Secondly, we used natural dye sensitizers, which possess ...
Probing The Unfolding And The Stability Of The Last Four Metal Binding Domains Of Wilson Disease Protein Using Circular Dichroism And Novel Spectroscopic Techniques, Ibtesam Yaseen Alja’Afreh
Wilson disease protein is a copper-transporting P1B type ATPase. It has large N-terminal copper binding domain which is composed of six homologous sub-domains. Each of these six domains is ~72 residues and connected to one another by linking regions of various lengths. They all possess similar ferrodoxin fold, and metal-binding motif, MXCXXC.
The need of having six metal binding domains and the manner in which they are communicating with each other is not well understood. To better understand how the last four metal binding domains function, I pursued a detailed biophysical characterization of these domains. Using molecular biology I ...
Mimicking Metabolism Of A Reversed Chloroquine Antimalarial, 2014 Portland State University
Mimicking Metabolism Of A Reversed Chloroquine Antimalarial, Kelsie Lynn Kendrick
Dissertations and Theses
The aim of this study was to elucidate the oxidation products of a candidate antimalarial drug, PL69, using a porphyrin system and to determine the accuracy of the oxidation products produced, as compared to what is expected in metabolism. PL69 is a reversed chloroquine (RCQ) that is active against chloroquine resistant malaria. Porphyrin oxidation systems have been shown to mimic in vitro enzymatic metabolism reactions. PL69 and its known metabolite, PL16, were incubated with the porphyrin system, and then the oxidation products were collected and separated by HPLC. The oxidation products were characterized by NMR and mass spectrometry and compared ...
Discovery And Characterization Of A Potent And Selective Inhibitory Of Aedes Aegypti Inward Rectifier Potassium Channels, Matthew F. Rouhier, Rene Raphemot, Daniel R. Swale, Emily Days, C. David Weaver, Kimberly M. Lovell, Leah C. Konkel, Darren W. Engers, Sean F. Bollinger, Corey Hopkins, Peter M. Piermarini, Jerod S. Denton
Vector-borne diseases such as dengue fever and malaria, which are transmitted by infected female mosquitoes, affect nearly half of the world's population. The emergence of insecticide-resistant mosquito populations is reducing the effectiveness of conventional insecticides and threatening current vector control strategies, which has created an urgent need to identify new molecular targets against which novel classes of insecticides can be developed. We previously demonstrated that small molecule inhibitors of mammalian Kir channels represent promising chemicals for new mosquitocide development. In this study, high-throughput screening of approximately 30,000 chemically diverse small-molecules was employed to discover potent and selective inhibitors ...
Peptide Arrays For Detecting Naphthenic Acids In Oil Sands Process Affected Water, 2014 Chapman University
Peptide Arrays For Detecting Naphthenic Acids In Oil Sands Process Affected Water, Kamaljit Kaur, Subir Bhattacharjee, Rajesh G. Pillai, Sahar Ahmed, Sarfuddin Azmi
Pharmacy Faculty Articles and Research
Naphthenic acids (NAs) are water-soluble components of petroleum. The characterization and quantification of NAs by analytical methods have proved quite challenging, whilst the toxic effects of these water-soluble compounds on a variety of organisms adversely affecting reproduction and steroid production is becoming apparent. In this study, we report a fluorescence-based competitive binding method for rapid sensing of the presence of NAs using cellulosic peptide array strips as sensors. The peptide array was designed from sequences derived from the estrogen receptor (ER). Several of these peptides were able to detect the presence of NAs at low micromolar (∼5 mg L−1 ...
Discovery Of Thienoquinolone Derivatives As Selective And Atp Non-Competitive Cdk5/P25 Inhibitors By Structure-Based Virtual Screening, Arindam Chatterjee, Stephen J. Cutler, Robert J. Doerksen, Ikhlas A. Khan, John S. Williamson
Office for Research Publications and Presentations
Calpain mediated cleavage of CDK5 natural precursor p35 causes a stable complex formation of CDK5/p25, which leads to hyperphosphorylation of tau. Thus inhibition of this complex is a viable target for numerous acute and chronic neurodegenerative diseases involving tau protein, including Alzheimer’s disease. Since CDK5 has the highest sequence homology with its mitotic counterpart CDK2, our primary goal was to design selective CDK5/p25 inhibitors targeting neurodegeneration. A novel structure-based virtual screening protocol comprised of e-pharmacophore models and virtual screening workflow was used to identify nine compounds from a commercial database containing 2.84 million compounds. An ATP ...
Hydrolytically Stable Analogues Of Sugar Phosphates And A Miniaturized In Situ Enzymatic Screen, 2014 University of Nebraska-Lincoln
Hydrolytically Stable Analogues Of Sugar Phosphates And A Miniaturized In Situ Enzymatic Screen, Xiang Fei
Student Research Projects, Dissertations, and Theses - Chemistry Department
The glmS riboswitch undergoes self-cleavage upon binding its metabolic product GlcN6P, thereby providing a negative feedback mechanism limiting translation of the glmS protein when GlcN6P is abundant. As a first step toward the development of novel antimicrobials, we have synthesized a series of GlcN6P analogues bearing phosphatase-inert surrogates in place of the natural phosphate ester functionality. The self-cleavage assay identified two such compounds that display significant riboswitch actuator activity; namely those bearing a 6-phosphonomethyl group or a 6-O-malonyl ether. These two analogues exhibit a 22-fold and a 27-fold higher catalytic efficiency, respectively, than does glucosamine. Docking experiments were ...
Poly(Ethylene Glycol)-Based Backbones With High Peptide Loading Capacities., 2014 Royal College of Surgeons in Ireland
Poly(Ethylene Glycol)-Based Backbones With High Peptide Loading Capacities., Aoife O'Connor, Jean-Noel Marsat, Annachiara Mitrugno, Tom Flahive, Niamh Moran, David Brayden, Marc Devocelle
Polymer-peptide conjugates are a promising class of compounds, where polymers can be used to overcome some of the limitations associated with peptides intended for therapeutic and/or diagnostic applications. Linear polymers such as poly(ethylene glycol) can be conjugated through terminal moieties and have therefore limited loading capacities. In this research, functionalised linear poly(ethylene glycol)s are utilised for peptide conjugation, to increase their potential loading capacities. These poly(ethylene glycol) derivatives are conjugated to peptide sequences containing representative side-chain functionalised amino acids, using different conjugation chemistries, including copper-catalysed azide-alkyne cycloaddition, amide coupling and thiol-ene reactions. Conjugation of a ...
Computational Survey Of Peptides Derived From Disulphide-Bonded Protein Loops That May Serve As Mediators Of Protein-Protein Interactions., Fergal J. Duffy, Marc Devocelle, David R. Croucher, Denis C. Shields
BACKGROUND: Bioactive cyclic peptides derived from natural sources are well studied, particularly those derived from non-ribosomal synthetases in fungi or bacteria. Ribosomally synthesised bioactive disulphide-bonded loops represent a large, naturally enriched library of potential bioactive compounds, worthy of systematic investigation.
RESULTS: We examined the distribution of short cyclic loops on the surface of a large number of proteins, especially membrane or extracellular proteins. Available three-dimensional structures highlighted a number of disulphide-bonded loops responsible for the majority of the likely binding interactions in a variety of protein complexes, due to their location at protein-protein interfaces. We find that disulphide-bonded loops at ...
Upgrading Malic Acid To Bio-Based Benzoates Via A Diels–Alder-Initiated Sequence With The Methyl Coumalate Platform, Jennifer J. Lee, Gerald R. Pollock Iii, Donald Mitchell, Lindsay Kasuga, George A. Kraus
The conversion of naturally-occurring malic acid to the 2-pyrone methyl coumalate was optimized using a variety of acid catalysts. Coupling methyl coumalate with electron-rich dienophiles in an inverse electron-demand Diels–Alder (IEDDA)/decarboxylation/elimination domino sequence resulted in an investigation of the scope and limitations of the methodology. The thermal, metal-free, and one-pot procedure allows regioselective access to diverse aromatic compounds including tricyclic, biphenyl, and pyridinyl systems for elaboration. A comparison with analogous pyrones demonstrates the striking efficacy of methyl coumalate as a versatile platform for the generation of biorenewable functionalized benzoates.