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2011

Biochemistry, Biophysics, and Structural Biology

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Full-Text Articles in Chemistry

Reactions With Platinum (Ll) Complexes And Selenium-Containing Amino Acids, Stephanie Robey Dec 2011

Reactions With Platinum (Ll) Complexes And Selenium-Containing Amino Acids, Stephanie Robey

Mahurin Honors College Capstone Experience/Thesis Projects

We have reacted [Pt(Me4en)(D2O)2]2+ [Me4En=N,N,N’N’-tetramethylethylenediamine] with Selenomethionine (SeMet), Methionine (Met), and Methylselenocysteine (MeSeCys). When MeSeCys was reacted with [Pt(Me4en)(D2O)2]2+, we observed both stereoisomers of Se,N chelates, as well as [Pt(Me4en)(MeSeCys)Cl]+ from ­1­H NMR Spectroscopy; the latter formed due to the presence of Cl- in the solution. Both isomers of the chelate seemed to form proportionally to one another, not favoring a specific stereoisomer. Eventually the [Pt(Me4en)(MeSeCys)Cl]+ products became Se,N chelates. We incubated SeMet with …

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Exploring The Roles Of Nucleobase Desolvation And Shape Complementarity During The Misreplication Of O6-Methylguanine, Delia Chavarria, Andrea Ramos Serrano, Ichiro Hirao, Anthony J. Berdis Sep 2011

Exploring The Roles Of Nucleobase Desolvation And Shape Complementarity During The Misreplication Of O6-Methylguanine, Delia Chavarria, Andrea Ramos Serrano, Ichiro Hirao, Anthony J. Berdis

Chemistry Faculty Publications

O6-methylguanine is a miscoding DNA lesion arising from the alkylation of guanine. This report uses the bacteriophage T4 DNA polymerase as a model to probe the roles hydrogen-bonding interactions, shape/size, and nucleobase desolvation during the replication of this miscoding lesion. This was accomplished by using transient kinetic techniques to monitor the kinetic parameters for incorporating and extending natural and non-natural nucleotides. In general, the efficiency of nucleotide incorporation does not depend on the hydrogen-bonding potential of the incoming nucleotide. Instead, nucleobase hydrophobicity and shape complementarity appear to be the preeminent factors controlling nucleotide incorporation. In addition, shape complementarity plays a …

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Rna Oxidation Adducts 8-Ohg And 8-Oha Change With Aβ42 Levels In Late-Stage Alzheimer's Disease, Adam M. Weidner, Melissa A. Bradley, Tina L. Beckett, Dana M. Niedowicz, Amy L.S. Dowling, Sergey V. Matveev, Harry Levine, Mark A. Lovell, M. Paul Murphy Sep 2011

Rna Oxidation Adducts 8-Ohg And 8-Oha Change With Aβ42 Levels In Late-Stage Alzheimer's Disease, Adam M. Weidner, Melissa A. Bradley, Tina L. Beckett, Dana M. Niedowicz, Amy L.S. Dowling, Sergey V. Matveev, Harry Levine, Mark A. Lovell, M. Paul Murphy

Sanders-Brown Center on Aging Faculty Publications

While research supports amyloid-β (Aβ) as the etiologic agent of Alzheimer's disease (AD), the mechanism of action remains unclear. Evidence indicates that adducts of RNA caused by oxidation also represent an early phenomenon in AD. It is currently unknown what type of influence these two observations have on each other, if any. We quantified five RNA adducts by gas chromatography/mass spectroscopy across five brain regions from AD cases and age-matched controls. We then used a reductive directed analysis to compare the RNA adducts to common indices of AD neuropathology and various pools of Aβ. Using data from four disease-affected brain …

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The Nucleotide Exchange Factor Ric-8a Is A Chaperone For The Conformationally Dynamic Nucleotide-Free State Of G Alpha I1, Celestine J. Thomas, Klara Briknarova, Jonathan K. Hilmer, Navid Movahed, Brian Bothner, John P. Sumida, Gregory G. Tall, Stephen R. Sprang Aug 2011

The Nucleotide Exchange Factor Ric-8a Is A Chaperone For The Conformationally Dynamic Nucleotide-Free State Of G Alpha I1, Celestine J. Thomas, Klara Briknarova, Jonathan K. Hilmer, Navid Movahed, Brian Bothner, John P. Sumida, Gregory G. Tall, Stephen R. Sprang

Chemistry and Biochemistry Faculty Publications

Heterotrimeric G protein alpha subunits are activated upon exchange of GDP for GTP at the nucleotide binding site of G alpha, catalyzed by guanine nucleotide exchange factors (GEFs). In addition to transmembrane G protein-coupled receptors (GPCRs), which act on G protein heterotrimers, members of the family cytosolic proteins typified by mammalian Ric-8A are GEFs for Gi/q/12/13-class G alpha subunits. Ric-8A binds to G alpha.GDP, resulting in the release of GDP. The Ric-8A complex with nucleotide-free G alpha i1 is stable, but dissociates upon binding of GTP to G alpha i1. To gain insight into the mechanism of Ric-8A-catalyzed GDP release …

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Thermal-Initiated Hydroxyethyl Methacrylate Functionalization Of Multiwalled Carbon Nanotubes, Greg Curtzwiler, Philip Costanzo, Ray Fernando, Jeffrey E. Danes, Keith Vorst Jul 2011

Thermal-Initiated Hydroxyethyl Methacrylate Functionalization Of Multiwalled Carbon Nanotubes, Greg Curtzwiler, Philip Costanzo, Ray Fernando, Jeffrey E. Danes, Keith Vorst

Chemistry and Biochemistry

Multiwalled-carbon nanotubes (MWCNTs) were functionalized via thermoinitiated free radical polymerization of 2-hydroxyethyl methacrylate (HEMA) using benzoyl peroxide. Tip sonication was used during the polymerization reaction to separate agglomerated nanotubes. The functionalization was confirmed by control experiments and attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR). Differential scanning calorimetry indicated that the addition of poly(HEMA)-MWCNTs to a two-component polyurethane coating will have little effect on the glass transition temperature of the coating. The poly(HEMA)-functionalized MWCNTs formed large colloidal structures of highly dispersed nanotubes in both the nonsheared and sheared coatings as determined by atomic force microscopy. This study determined a quick …

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Quantifying The Flux Of Caco3 And Organic Carbon From The Surface Ocean Using In Situ Measurements Of O-2, N-2, Pco(2), And Ph, Steven Emerson, Christopher Sabine, Meghan F. Cronin, Richard Feely, Sarah E. Cullison Gray, Michael Degrandpre Jul 2011

Quantifying The Flux Of Caco3 And Organic Carbon From The Surface Ocean Using In Situ Measurements Of O-2, N-2, Pco(2), And Ph, Steven Emerson, Christopher Sabine, Meghan F. Cronin, Richard Feely, Sarah E. Cullison Gray, Michael Degrandpre

Chemistry and Biochemistry Faculty Publications

Ocean acidification from anthropogenic CO2 has focused our attention on the importance of understanding the rates and mechanisms of CaCO3 formation so that changes can be monitored and feedbacks predicted. We present a method for determining the rate of CaCO3 production using in situ measureme nts of fCO(2) and pH in surface waters of the eastern subarctic Pacific Ocean. These quantities were determined on a surface mooring every 3 h for a period of about 9 months in 2007 at Ocean Station Papa (50 degrees N, 145 degrees W). We use the data in a simple surface ocean, mass balance …

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Co2 Production In The Bromate-1,4-Cyclohexanedione Oscillatory Reaction, Jiamin Feng, James R. Green, Samuel A. Johnson, Jichang Wang Jun 2011

Co2 Production In The Bromate-1,4-Cyclohexanedione Oscillatory Reaction, Jiamin Feng, James R. Green, Samuel A. Johnson, Jichang Wang

Chemistry and Biochemistry Publications

NMR and GC/MS spectroscopy of the organic extracts of the oscillatory bromate-1,4-cyclohexanedione reaction illustrate the presence of ring-opening products 5-(dibromomethylene)-2(5H)-furanone, (E)-5,5,5-tribromo-4-oxo-2-pentenoic acid, and dibromoacetic acid, particularly at elevated temperatures. The loss of a carbon atom from the six-membered ring after ring opening led to gas formation and such a process became more vigorous at >60 °C, with the direct observation of bubbles in a stirred batch reactor. Gravimetric experiments confirm that the amount of carbon dioxide gas produced increases rapidly with reaction temperature. Parallel experiments suggest that the ring-opening process involves the oxidation of brominated benzoquinones by bromate. Copyright © …

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Direct Imaging Of Two-State Dynamics On The Amorphous Silicon Surface, S. Ashtekar, Gregory E. Scott, J. Lyding, M. Gruebele Jun 2011

Direct Imaging Of Two-State Dynamics On The Amorphous Silicon Surface, S. Ashtekar, Gregory E. Scott, J. Lyding, M. Gruebele

Chemistry and Biochemistry

Amorphous silicon is an important material, amidst a debate whether or not it is a glass. We produce amorphous Si surfaces by ion bombardment and vapor growth, and image discrete Si clusters which hop by two-state dynamics at 295 K. Independent of surface preparation, these clusters have an average diameter of ~5 atoms. Given prior results for metallic glasses, we suggest that this cluster size is a universal feature. The hopping activation free energy of 0.93 ± 0.15 eV is rather small, in agreement with a previously untested surface glass model. Hydrogenation quenches the two-state dynamics, apparently by increasing surface …

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Lipid Peroxidation And Neurodegenerative Disease, Tanea Reed Jun 2011

Lipid Peroxidation And Neurodegenerative Disease, Tanea Reed

Chemistry Faculty and Staff Scholarship

Lipid peroxidation is a complex process involving the interaction of oxygen-derived free radicals with polyunsaturated fatty acids, resulting in a variety of highly reactive electrophilic aldehydes. Since 1975, lipid peroxidation has been extensively studied in a variety of organisms. As neurodegenerative diseases became better understood, research establishing a link between this form of oxidative damage, neurodegeneration, and disease has provided a wealth of knowledge to the scientific community. With the advent of proteomics in 1995, the identification of biomarkers for neurodegenerative disorders became of paramount importance to better understand disease pathogenesis and develop potential therapeutic strategies. This review focuses on …

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Applications Of Argentation Solid Phase Extraction To The Capsaicinoids: Purification Of Commercial Standards And Isolation Of Homodihydrocapsaicin (8-Methyl) From 'Bhut Jolokia', Robert Q. Thompson, Kathleen Loa Jun 2011

Applications Of Argentation Solid Phase Extraction To The Capsaicinoids: Purification Of Commercial Standards And Isolation Of Homodihydrocapsaicin (8-Methyl) From 'Bhut Jolokia', Robert Q. Thompson, Kathleen Loa

Faculty & Staff Scholarship

Argentation solid phase extraction was employed to purify commercial standards of capsaicin (6-ene-8-methyl) and dihydrocapsaicin (8-methyl). The purity was improved from 96.7% to 99.6% and from 89% to 96%, respectively, with 75% and 60% yield, respectively. Reversed phase solid phase extraction, argentation solid phase extraction, and preparative liquid chromatography with a C30 phase were used to isolate capsaicinoids from the fruits of 'Bhut Jolokia' peppers. The compounds capsaicin (6-ene-8-methyl) and dihydrocapsaicin (8-methyl) comprised 74% and 21% of the total mass of capsaicinoids. respectively. The remaining 5% of the capsaicinoids mass included the compounds: nordihydrocapsaicin (7-methyl), N-vanillylnonanamide, two homocapsaicin isomers, N-vanillyldecanamide, …

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Tension Directly Stabilizes Reconstituted Kinetochore-Microtubule Attachments, Bungo Akiyoshi, Krishna K. Sarangapani, Andrew F. Powers, Christian R. Nelson, Steve Reichow, Hugo Arellano-Santoyo, Tamir Gonen, Jeffrey A. Ranish, Charles L. Asbury, Sue Biggins Jun 2011

Tension Directly Stabilizes Reconstituted Kinetochore-Microtubule Attachments, Bungo Akiyoshi, Krishna K. Sarangapani, Andrew F. Powers, Christian R. Nelson, Steve Reichow, Hugo Arellano-Santoyo, Tamir Gonen, Jeffrey A. Ranish, Charles L. Asbury, Sue Biggins

Chemistry Faculty Publications and Presentations

Kinetochores are macromolecular machines that couple chromosomes to dynamic microtubule tips during cell division, thereby generating force to segregate the chromosomes. Accurate segregation depends on selective stabilization of correct ‘bi-oriented’ kinetochore-microtubule attachments, which come under tension due to opposing forces exerted by microtubules. Tension is thought to stabilize these bi-oriented attachments indirectly, by suppressing the destabilizing activity of a kinase, Aurora B. However, a complete mechanistic understanding of the role of tension requires reconstitution of kinetochore-microtubule attachments for biochemical and biophysical analyses in vitro. Here we show that native kinetochore particles retaining the majority of kinetochore proteins can be …

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The Exonuclease Activity Of Hpmc2 Is Required For Transcriptional Regulation Of The Qr Gene And Repair Of Estrogen-Induced Abasic Sites, N. Krishnamurthy, C. R. Ngam, Anthony J. Berdis, M. M. Montano May 2011

The Exonuclease Activity Of Hpmc2 Is Required For Transcriptional Regulation Of The Qr Gene And Repair Of Estrogen-Induced Abasic Sites, N. Krishnamurthy, C. R. Ngam, Anthony J. Berdis, M. M. Montano

Chemistry Faculty Publications

We have previously reported that the expression of antioxidative stress enzymes is upregulated by trans-hydroxytamoxifen (TOT) in breast epithelial cell lines providing protection against estrogen-induced DNA damage. This regulation involves Estrogen Receptor β (ERβ) recruitment to the Electrophile Response Element (EpRE) and a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2). We have also demonstrated that ERβ and hPMC2 are required for TOT-dependent recruitment of poly (ADP-ribose) polymerase 1 (PARP-1) and Topoisomerase IIβ (Topo IIβ) to the EpRE. Sequence analysis reveals that the C-terminus of hPMC2 encodes a putative exonuclease domain. Using in vitro kinetic assays, …

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Pcr Amplification Of Trypanosoma Cruzi - Specific Dna From Raccoon Blood Samples, Colin Moss May 2011

Pcr Amplification Of Trypanosoma Cruzi - Specific Dna From Raccoon Blood Samples, Colin Moss

Mahurin Honors College Capstone Experience/Thesis Projects

The parasitic protist Trypanosoma cruzi is the causative agent of Chagas Disease. Chagas Disease causes greater than 15,000 deaths each year, and nearly 28 million people are believed to be at risk of infection in Central and South America. This parasite has been described in many mammalian host species and has also been described in the United States. The purpose of this study was to attempt to use PCR to amplify T. cruzi-specific DNA directly from blood samples obtained from raccoons (Procyon lotor) trapped in Warren and Barren Counties of Kentucky in 2007 and 2008. DNA was …

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Characterization Of Ceriporiopsis Subvermispora Bicupin Oxalate Oxidase Expressed In Pichia Pastoris, Patricia Moussatche, Alexander Angerhofer, Witcha Imaram, Eric Hoffer, Kelsey Uberto, Christopher Brooks, Crystal Bruce, Daniel Sledge, Nigel G. J. Richards, Ellen W. Moomaw May 2011

Characterization Of Ceriporiopsis Subvermispora Bicupin Oxalate Oxidase Expressed In Pichia Pastoris, Patricia Moussatche, Alexander Angerhofer, Witcha Imaram, Eric Hoffer, Kelsey Uberto, Christopher Brooks, Crystal Bruce, Daniel Sledge, Nigel G. J. Richards, Ellen W. Moomaw

Faculty and Research Publications

Oxalate oxidase (E.C. 1.2.3.4) catalyzes the oxygen-dependent oxidation of oxalate to carbon dioxide in a reaction that is coupled with the formation of hydrogen peroxide. Although there is currently no structural information available for oxalate oxidase fromCeriporiopsis subvermispora (CsOxOx), sequence data and homology modeling indicate that it is the first manganese-containing bicupin enzyme identified that catalyzes this reaction. Interestingly, CsOxOx shares greatest sequence homology with bicupin microbial oxalate decarboxylases (OxDC). We show that CsOxOx activity directly correlates with Mn content and other metals do not appear to be able to support catalysis. EPR spectra indicate that the Mn is present …

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An Assessment Of Stable Hydrogen-Isotope Analysis Methods To Assign Geographic Origin To Migratory Red-Tailed Hawks (Buteo Jamaicensis), Carla Marie Ahlschwede May 2011

An Assessment Of Stable Hydrogen-Isotope Analysis Methods To Assign Geographic Origin To Migratory Red-Tailed Hawks (Buteo Jamaicensis), Carla Marie Ahlschwede

Department of Environmental Studies: Undergraduate Student Theses

Stable-hydrogen isotopes are becoming an increasingly popular method of studying migratory birds, though sample preparation methods may affect results. In this study I examined feathers from red-tailed hawks (Buteo jamaicensis) to determine the relationship between measure of δD due to inter-feather variation or drying methods, assessed the accuracy of results by using two birds of known-origin and estimated possible natal origins of migratory red-tailed hawks. Two feathers per individual were taken from 81 wild hawks caught at Hitchcock Nature Center near Crescent IA and from 2 rescued red-tailed hawks, Raptor Recovery Nebraska near Eagle, NE. 119 of the …

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Epistatic Roles For Pseudomonas Aeruginosa Muts And Dinb (Dna Pol Iv) In Coping With Reactive Oxygen Species-Induced Dna Damage, Laurie H. Sanders, Babho Devadoss, Geraldine V. Raja, Jaime O'Connor, Shengchang Su, Daniel J. Wozniak, Daniel J. Hassett, Anthony J. Berdis, Mark D. Sutton Apr 2011

Epistatic Roles For Pseudomonas Aeruginosa Muts And Dinb (Dna Pol Iv) In Coping With Reactive Oxygen Species-Induced Dna Damage, Laurie H. Sanders, Babho Devadoss, Geraldine V. Raja, Jaime O'Connor, Shengchang Su, Daniel J. Wozniak, Daniel J. Hassett, Anthony J. Berdis, Mark D. Sutton

Chemistry Faculty Publications

Pseudomonas aeruginosa is especially adept at colonizing the airways of individuals afflicted with the autosomal recessive disease cystic fibrosis (CF). CF patients suffer from chronic airway inflammation, which contributes to lung deterioration. Once established in the airways, P. aeruginosa continuously adapts to the changing environment, in part through acquisition of beneficial mutations via a process termed pathoadaptation. MutS and DinB are proposed to play opposing roles in P. aeruginosa pathoadaptation: MutS acts in replication-coupled mismatch repair, which acts to limit spontaneous mutations; in contrast, DinB (DNA polymerase IV) catalyzes error-prone bypass of DNA lesions, contributing to mutations. As part of …

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Dicarbonyldichloridobis(Trimethylphosphane)Iron(Ii)–Carbonyldichloridotris(Trimethylphosphane)Iron(Ii)–Tetrahydrofuran (1/1/2), Nigam Rath, Meghan Stouffer, Matthew Janssen, John Bleeke Apr 2011

Dicarbonyldichloridobis(Trimethylphosphane)Iron(Ii)–Carbonyldichloridotris(Trimethylphosphane)Iron(Ii)–Tetrahydrofuran (1/1/2), Nigam Rath, Meghan Stouffer, Matthew Janssen, John Bleeke

Chemistry & Biochemistry Faculty Works

The asymmetric unit of the title crystal, [FeCl2(C3H9P)3(CO)]·[FeCl2(C3H9P)2(CO)2]·2C4H8O, contains half mol­ecules of the two closely related FeII complexes lying on mirror planes and a tetra­hydro­furan solvent mol­ecule, one C atom of which is disordered over two sets of sites with site occupancy factors 0.633 (9) and 0.367 (9). In both FeII complex mol­ecules, a distorted octa­hedral coordination geometry has been observed around the Fe atoms. Weak intermolecular C-H...O inter­actions are observed in the crystal structure.

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Dehydrotropylium-Co2(Co)6 Ion. Generation, Reactivity And Evaluation Of Cation Stability, Sheida Amiralaei, James Gauld, James R. Green Apr 2011

Dehydrotropylium-Co2(Co)6 Ion. Generation, Reactivity And Evaluation Of Cation Stability, Sheida Amiralaei, James Gauld, James R. Green

Chemistry and Biochemistry Publications

The dehydrotropylium–Co2(CO)6 ion was generated by the action of HBF4 or BF3⋅OEt2 on the corresponding cycloheptadienynol complex, which in turn has been prepared in four steps from a known diacetoxycycloheptenyne complex. The reaction of the cycloheptadienynol complex via the dehydrotropylium–Co2(CO)6 ion with several nucleophiles results in substitution reactions with reactive nucleophiles (N>1) under normal conditions, and a radical dimerisation reaction in the presence of less reactive nucleophiles. Competitive reactions of the cycloheptadienynol complex with an acyclic trienynol complex show no preference for generation of the dehydrotropylium–Co2 …

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Synthesis Of ‘Spacer’-Naproxen [2-(6-Methoxybiphenylen-2-Yl)Propanoic Acid] And -Isonaproxen [2-(7-Methoxybiphenylen-2-Yl)Propanoic Acid], Juan A. González Gómez, James R. Green, Peter C. Vollhardt Apr 2011

Synthesis Of ‘Spacer’-Naproxen [2-(6-Methoxybiphenylen-2-Yl)Propanoic Acid] And -Isonaproxen [2-(7-Methoxybiphenylen-2-Yl)Propanoic Acid], Juan A. González Gómez, James R. Green, Peter C. Vollhardt

Chemistry and Biochemistry Publications

The CpCo(CO)2-catalyzed cocyclization of 1,2-diethynyl- 4-methoxybenzene with alkynes can be applied to the synthesis of ‘spacer’-naproxen [2-(6-methoxybiphenylen-2-yl)propanoic acid] and its 7-methoxy isomer, ‘spacer’-isonaproxen. While unsymmetrical alkynes are incorporated without regioselectivity, the methoxy group in 6-methoxy-2,3-bis(trimethylsilyl)biphenylene directs electrophiles to C-3, thus allowing for regiochemical differentiation between the 2- and 3-positions.

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Organometallic Iron(Iii)-Salophene Exerts Cytotoxic Properties In Neuroblastoma Cells Via Mapk Activation And Ros Generation, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Richard G. Moore, Laurent Brard, Thilo S. Lange Apr 2011

Organometallic Iron(Iii)-Salophene Exerts Cytotoxic Properties In Neuroblastoma Cells Via Mapk Activation And Ros Generation, Kyu Kwang Kim, Rakesh K. Singh, Robert M. Strongin, Richard G. Moore, Laurent Brard, Thilo S. Lange

Chemistry Faculty Publications and Presentations

The objective of the present study was to investigate the specific effects of Iron(III)-salophene (Fe-SP) on viability, morphology, proliferation, cell cycle progression, ROS generation and pro-apoptotic MAPK activation in neuroblastoma (NB) cells. A NCI-DTP cancer screen revealed that Fe-SP displayed high toxicity against cell lines of different tumor origin but not tumor type-specificity. In a viability screen Fe-SP exhibited high cytotoxicity against all three NB cell lines tested. The compound caused cell cycle arrest in G1 phase, suppression of cells progressing through S phase, morphological changes, disruption of the mitochondrial membrane depolarization potential, induction of apoptotic markers as well as …

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Her2 Targeted Molecular Mr Imaging Using A De Novo Designed Protein Contrast Agent, Jingjuan Qiao, Shunyi Li, Lixia Wei, Jie Jiang, Robert Long, Hui Mao, Ling Wei, Liya Wang, Hua Yang, Hans E. Grossniklaus, Zhi-Ren Liu, Jenny J. Yang Mar 2011

Her2 Targeted Molecular Mr Imaging Using A De Novo Designed Protein Contrast Agent, Jingjuan Qiao, Shunyi Li, Lixia Wei, Jie Jiang, Robert Long, Hui Mao, Ling Wei, Liya Wang, Hua Yang, Hans E. Grossniklaus, Zhi-Ren Liu, Jenny J. Yang

Chemistry Faculty Publications

The application of magnetic resonance imaging (MRI) to non-invasively assess disease biomarkers has been hampered by the lack of desired contrast agents with high relaxivity, targeting capability, and optimized pharmacokinetics. We have developed a novel MR imaging probe targeting to HER2, a biomarker for various cancer types and a drug target for anti-cancer therapies. This multimodal HER20targeted MR imaging probe integrates a de novo designed protein contrast agent with a high affinity HER2 affibody and a near IR fluorescent dye. Our probe can differentially monitor tumors with different expression levels of HER2 in both human cell lines and xenograft mice …

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Transformation Of Fusarium Verticillioides With A Polyketide Gene Cluster Isolated From A Fungal Endophyte Activates The Biosynthesis Of Fusaric Acid, Yunxuan Xie, Wei Zhang, Yaoyao Li, Mingzi Wang, Ronald Cerny, Yue Shen, Liangcheng Du Mar 2011

Transformation Of Fusarium Verticillioides With A Polyketide Gene Cluster Isolated From A Fungal Endophyte Activates The Biosynthesis Of Fusaric Acid, Yunxuan Xie, Wei Zhang, Yaoyao Li, Mingzi Wang, Ronald Cerny, Yue Shen, Liangcheng Du

Liangcheng Du Publications

A large number of bioactive natural products have been isolated from plant endophytic fungi. However, molecular mechanisms for the biosynthesis of these metabolites have lagged behind because genetic and biochemical studies are difficult to perform within many of the endophytes. In this work, we describe our attempt to express a putative mycoepoxydiene (MED) biosynthetic gene cluster in Fusarium verticillioides, which has a well-developed genetic system for the study fungal polyketide biosynthesis. MED was isolated from Phomopsis sp. A123, a fungal endophyte of the mangrove plant, Kandelia candel. It has several unusual structural features and interesting biological activities. Integration of …

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Quantifying The Energetic Contributions Of Desolvation And Π-Electron Density During Translesion Dna Synthesis, Edward A. Motea, Irene Lee, Anthony J. Berdis Mar 2011

Quantifying The Energetic Contributions Of Desolvation And Π-Electron Density During Translesion Dna Synthesis, Edward A. Motea, Irene Lee, Anthony J. Berdis

Chemistry Faculty Publications

This report examines the molecular mechanism by which high-fidelity DNA polymerases select nucleotides during the replication of an abasic site, a non-instructional DNA lesion. This was accomplished by synthesizing several unique 5-substituted indolyl 2′-deoxyribose triphosphates and defining their kinetic parameters for incorporation opposite an abasic site to interrogate the contributions of π-electron density and solvation energies. In general, the Kd, app values for hydrophobic non-natural nucleotides are ∼10-fold lower than those measured for isosteric hydrophilic analogs. In addition, kpol values for nucleotides that contain less π-electron densities are slower than isosteric analogs possessing higher degrees of π-electron density. The differences …

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Formation And Stability Of Atmospherically Relevant Isoprene-Derived Organosulfates And Organonitrates, Adam I. Darer, Neil C. Cole-Filipiak, Alison E. O'Connor, Matthew J. Elrod Mar 2011

Formation And Stability Of Atmospherically Relevant Isoprene-Derived Organosulfates And Organonitrates, Adam I. Darer, Neil C. Cole-Filipiak, Alison E. O'Connor, Matthew J. Elrod

Faculty & Staff Scholarship

Isoprene is the precursor for number of alcohol, organosulfate, and organonitrate species observed in ambient secondary organic aerosol (SOA). Recent laboratory and field work has suggested that isoprene-derived epoxides may be crucial intermediates that can explain the existence of these compounds in SOA. To confirm this hypothesis, the specific hydroxy epoxides observed in gas phase isoprene photooxidation experiments (as well as several other related species) were synthesized and the bulk phase aqueous reactions of these species in the presence of sulfate and nitrate were studied via nuclear magnetic resonance (NMR) techniques. The results indicate that both primary and tertiary organosulfates …

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Polycationic Glycosides, Robert Engel, Ishrat Ghani, Diego Montenegro, Marie Thomas, Barbara Klaritch-Vrana, Alejandra Castaño, Laura Friedman, Jay Leb, Leah Rothman, Heidi Lee, Craig Capodiferro, Daniel Ambinder, Eve Cere, Christopher Awad, Faiza Sheikh, Jaimelee Rizzo, Lisa-Marie Nisbett, Erika Testani, Karin Melkonian Feb 2011

Polycationic Glycosides, Robert Engel, Ishrat Ghani, Diego Montenegro, Marie Thomas, Barbara Klaritch-Vrana, Alejandra Castaño, Laura Friedman, Jay Leb, Leah Rothman, Heidi Lee, Craig Capodiferro, Daniel Ambinder, Eve Cere, Christopher Awad, Faiza Sheikh, Jaimelee Rizzo, Lisa-Marie Nisbett, Erika Testani, Karin Melkonian

Publications and Research

Cationic lipids have long been known to serve as antibacterial and antifungal agents. Prior efforts with attachment of cationic lipids to carbohydrate-based surfaces have suggested the possibility that carbohydrate-attached cationic lipids might serve as antibacterial and antifungal pharmaceutical agents. Toward the understanding of this possibility, we have synthesized several series of cationic lipids attached to a variety of glycosides with the intent of generating antimicrobial agents that would meet the requirement for serving as a pharmaceutical agent, specifically that the agent be effective at a very low concentration as well as being biodegradable within the organism being treated. The initial …

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Pharmacological Chaperoning In Fabry Disease, Jerome Rogich Jan 2011

Pharmacological Chaperoning In Fabry Disease, Jerome Rogich

Masters Theses 1911 - February 2014

Fabry Disease is an X-­‐linked lysosomal storage disorder characterized by a variety of symptoms including hypohydrosis, seizures, cardiac abnormalities, skin lesions, and chronic pain. These symptoms stem from a lack of functional endogenous α-­‐ Galactosidase A (α-­GAL), which leads to an accrual of its natural substrate. The severity of the disease symptoms can be directly correlated with the amount of residual enzyme activity. It has been shown that an imino sugar, 1-deoxygalactonojirimycin (DGJ), can increase enzymatic activity and clear excess substrate. This pH-­‐dependent chaperoning phenomenon is believed to arise from the presence of aspartic acid 170 in the active site. …

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Better Biomolecule Thermodynamics From Kinetics, Kiran Girdhar, Gregory Scott, Yann R. Chemla, Martin Gruebele Jan 2011

Better Biomolecule Thermodynamics From Kinetics, Kiran Girdhar, Gregory Scott, Yann R. Chemla, Martin Gruebele

Chemistry and Biochemistry

Protein stability is measured by denaturation: When solvent conditions are changed (e.g., temperature, denaturant concentration, or pH) the protein population switches between thermodynamic states. The resulting denaturation curves have baselines. If the baselines are steep, nonlinear, or incomplete, it becomes difficult to characterize protein denaturation. Baselines arise because the chromophore probing denaturation is sensitive to solvent conditions, or because the thermodynamic states evolve structurally when solvent conditions are changed, or because the barriers are very low (downhill folding). Kinetics can largely eliminate such baselines: Relaxation of chromophores, or within thermodynamic states, is much faster than the transition over activation …

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Microfluidic Paper-Based Analytical Devices: From Pocket To Paper-Based Elisa, Andres W. Martinez Jan 2011

Microfluidic Paper-Based Analytical Devices: From Pocket To Paper-Based Elisa, Andres W. Martinez

Chemistry and Biochemistry

Microfluidic paper-based analytical devices (microPADs) began as a simple idea with an ambitious goal. The idea was to make microfluidic devices out of paper instead of plastic or glass. The goal was to develop low-cost and portable paper-based diagnostic devices to improve healthcare in developing countries. Over the past 6 years, many developments have been made in the emerging field of paper-based microfluidic devices. Reviewing the development of these devices in the Whitesides group at Harvard University (Cambridge, MA, USA) can provide some insight into the future of the field and encourage scientists from a variety of backgrounds to contribute …

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A Bulk Water-Dependent Desolvation Energy Model For Analyzing The Effects Of Secondary Solutes On Biological Equilibria, Daryl K. Eggers Jan 2011

A Bulk Water-Dependent Desolvation Energy Model For Analyzing The Effects Of Secondary Solutes On Biological Equilibria, Daryl K. Eggers

Faculty Publications, Chemistry

A new phenomenological model for interpreting the effects of solutes on biological equilibria is presented. The model attributes changes in equilibria to differences in the desolvation energy of the reacting species that, in turn, reflect changes in the free energy of the bulk water upon addition of secondary solutes. The desolvation approach differs notably from that of other solute models by treating the free energy of bulk water as a variable and by not ascribing the observed shifts in reaction equilibria to accumulation or depletion of solutes next to the surfaces of the reacting species. On the contrary, the partitioning …

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Crystallization And Preliminary X-Ray Crystallographic Analysis Of Ligand-Free And Arginine-Bound Forms Of Thermotoga Maritima Arginine-Binding Protein, Alessia Ruggiero, Jonathan D. Dattelbaum, Anna Pennacchio, Luisa Iozzion, Maria Staiano, Matthew S. Luchansky, Bryan S. Der, Rita Berisio, Sabato D'Auria, Luigi Vitagliano Jan 2011

Crystallization And Preliminary X-Ray Crystallographic Analysis Of Ligand-Free And Arginine-Bound Forms Of Thermotoga Maritima Arginine-Binding Protein, Alessia Ruggiero, Jonathan D. Dattelbaum, Anna Pennacchio, Luisa Iozzion, Maria Staiano, Matthew S. Luchansky, Bryan S. Der, Rita Berisio, Sabato D'Auria, Luigi Vitagliano

Chemistry Faculty Publications

The arginine-binding protein from Thermotoga maritima (TmArgBP) is an arginine-binding component of the ATP-binding cassette (ABC) transport system in this hyperthermophilic bacterium. This protein is endowed with an extraordinary stability towards thermal and chemical denaturation. Its structural characterization may provide useful insights for the clarification of structure– stability relationships and for the design of new biosensors. Crystallization trials were set up for both arginine-bound and ligand-free forms of TmArgBP and crystals suitable for crystallographic investigations were obtained for both forms. Ordered crystals of the arginine adduct of TmArgBP could only be obtained by using the detergent LDAO as an additive …

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