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Title: Effects of glycosylation on melanoma interactions with type IV collagen models.
Creator: Aukszi, Beatrix., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Tumor cells interact with basement membrane collagen at the site of extravasation through distinct cellular receptors, including the α2β1 and α3β1integrins. These receptors are known to be differentially expressed in metastatic tumors, relative to the normal cells, depending on tumor type and stage of progression. The binding sites within type IV collagen for the α2β1 andα3β1 integrins have been identified. Since both of the integinspecific sequences possess at least one glycosylated Hyl...
Show moreTumor cells interact with basement membrane collagen at the site of extravasation through distinct cellular receptors, including the α2β1 and α3β1integrins. These receptors are known to be differentially expressed in metastatic tumors, relative to the normal cells, depending on tumor type and stage of progression. The binding sites within type IV collagen for the α2β1 andα3β1 integrins have been identified. Since both of the integinspecific sequences possess at least one glycosylated Hyl residue, we questioned whether glycosylation could modulate integrin binding. Triple-helical peptides with and without Lys substituted by glycosylated Hyl for Lys543 and Lys540 from the human a1(IV)531-543 gene sequence (α3β integrin-specific) and Lys393 from the human a1(IV)382-393 gene sequence (α2β1 integrin-specific) were synthesized and utilized in the present study., Cellular response to these triple helical ligands was tested with a primary melanoma cell line, WM-115, and three highly metastatic melanoma cell lines , WM-266-4, M14#5, and SK-MEL-2. Cell adhesion and cell spreading assays yielded differing results depending on whether the ligands contained glycosylated Hyl residues or not. In general, a decrease in cellular affinity toward the ligands was observed when glycosylated Hyl was present. Differences in the levels of adhesion and spreading between cell lines representing different stages of melanoma were also observed. Neutral B-galactosidase activity was detected in all four cell lines. Enzymatic activity levels were comparable for the three metastatic cell lines, whereas distinctively higher activity was detected for cells originating from a primary lesion. This acitivity can signal the potential of tumor cells to enhance and recover their invasive abilities., The ability of each cell line to remove the galactose from the peptide ligands has been investigated, to test whether tumor cells can reestablish binding relationships between the α2β1 and α3β1 integrins and type IV collagen that are reduced by glycosylation.
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Date Issued: 2008
PURL: http://purl.flvc.org/FAU/186335
Subject Headings: Animal cell biotechnology, Combinatorial chemistry, Integrins, Research, Methodology, Cell adhesion molecules, Physiological effect
Format: Document (PDF)

Title: Synthesis, structural characterization and biological studies of organotin polyethers (Sn-O).
Creator: Barot, Girish Vallabhbhai., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin...
Show moreCancer is the second leading cause of death in the western world. In order to treat various types of cancer, platinum-based drugs are most widely employed as metal-containing chemotherapeutic agents. However, their clinical usage is hindered by toxic side effects, and by the emergence of drug resistance. Our focus was to replace platinum with less toxic metal like tin which can give better alternatives for cancer treatment. The major aim of our study was to synthesize novel organotin polyethers (Sn-O) which can be used to combat cancer. Preliminary results from our laboratory using organotin polyethers, that were synthesized by varying the structure of diols showed growth inhibition in Balb-3T3 cells. This study directly led us to hypothesize the two structural windows, first by changing the distance between diol and second, by presence of unsaturation in diols, the biological activity of organotin polyethers (Sn-O) can be enhanced significantly. Different series of polymeric compounds were synthesized based upon these two structural windows and the formation of products was validated using standard techniques like infrared spectroscopy (IR), light scattering photometer, matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and nuclear magnetic resonance (NMR). The synthesized polymers arrested the growth of cancer cell lines including bone, prostate, colon, breast, pancreas and lung cancer derived cell lines in vitro. In number of instances where chemotherapeutic index values of two and greater were found that these polymers are significantly more active against cancer cells than non-cancerous cells in culture., These results support the starting premise that the polymers may exhibit cancer cell selectivity. In general, it was found that the presence of unsaturation increased the probability that the polyether would inhibit the growth of various cancer cell lines. Further, in some cases, polyethers with short distances between the oxygen atoms showed a superior ability to inhibit the growth of various cancer cell lines in comparison to those with longer distances between the oxygen atoms. These results provide a framework for the discovery of novel cancer therapeutics.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/186672
Subject Headings: Organometallic polymers, Cancer, Molecular aspects, Apoptosis, Molecular aspects, Antineoplastic agents, Testing, Polymers in medicine
Format: Document (PDF)

Title: Studies towards a catalytic asymmetric isomerization of manganese complexed alkynes to allenes using chiral bases.
Creator: He, Chang., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The conversion of alkynyl carbonyls to allenyl carbonyls via manganese mediated coordination followed by a base-catalyzed isomerization was carried out using a range of chiral and achiral amine bases. Chiral amidine and chiral DBU derivatives were synthesized to carry out the isomerization enantioselectively. We employed HPLC equipped with a chiral column to determine the enantiomeric excess. We also proved that the mechanism of that the manganese-coordinated alkyne/allene rearrangement...
Show moreThe conversion of alkynyl carbonyls to allenyl carbonyls via manganese mediated coordination followed by a base-catalyzed isomerization was carried out using a range of chiral and achiral amine bases. Chiral amidine and chiral DBU derivatives were synthesized to carry out the isomerization enantioselectively. We employed HPLC equipped with a chiral column to determine the enantiomeric excess. We also proved that the mechanism of that the manganese-coordinated alkyne/allene rearrangement reaction involved an intermediate cumenolate. It was also confirmed that amine base with pKa lower than that of DBU (pKa = 13.6) would not carry out the isomerization. Alkoxy base were also used in isomerization and the mechanism was also investigated.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/192983
Subject Headings: Enzyme kinetics, Organometallic compounds, Synthesis, Asymmetric synthesis, Methathesis (Chemistry), Carbonyl compounds, Synthesis
Format: Document (PDF)

Title: Comparison of chemotaxonomic methods for the determination of periphyton community composition.
Creator: Browne, Jamie L., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Pigment-based chemotaxonomy uses relative amounts of photosynthetic pigments (biomarkers) within algae samples to determine the algal class composition of each sample. Chemotaxonomy has been applied successfully to phytoplankton communities, but its efficacy for periphyton has not yet been established. This study examined the ability of simultaneous linear equations (SLE), CHEMTAX, and the Bayesian Compositional Estimator (BCE) to determine algal class composition in Florida Everglades...
Show morePigment-based chemotaxonomy uses relative amounts of photosynthetic pigments (biomarkers) within algae samples to determine the algal class composition of each sample. Chemotaxonomy has been applied successfully to phytoplankton communities, but its efficacy for periphyton has not yet been established. This study examined the ability of simultaneous linear equations (SLE), CHEMTAX, and the Bayesian Compositional Estimator (BCE) to determine algal class composition in Florida Everglades periphyton. The methods were applied to artificial datasets, mixed lab cultures of known composition, and Everglades periphyton samples for which microscopic biovolume data was available. All methods were able to return accurate sample compositions for artificial data and mixed lab cultures. Correlation between pigment methods and microscopic results for natural periphyton samples was poor. SLE and CHEMTAX returned similar results for all samples while BCE performed less well.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2100582
Subject Headings: Water quality biological assessment, Periphyton, Water, Phosphorus content, Freshwater algae
Format: Document (PDF)

Title: Determination and evaluation of electrical properties of metal-containing condensation polymers.
Creator: Battin, Amitabh J., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Doped electrically conductive polymers are one of the critical materials that have allowed the current technological revolution. Essentially all of today's applications of doped conductive polymers involve vinyl-related polymers. While the application of conductive polymers is rapidly increasing, there is need for additional materials with different electrical behaviors. The current focus is on studying condensation polymers that contain a metal atom and the possibility of undergoing entire...
Show moreDoped electrically conductive polymers are one of the critical materials that have allowed the current technological revolution. Essentially all of today's applications of doped conductive polymers involve vinyl-related polymers. While the application of conductive polymers is rapidly increasing, there is need for additional materials with different electrical behaviors. The current focus is on studying condensation polymers that contain a metal atom and the possibility of undergoing entire chain delocalization of electrons. The different series of organometallic condensation polymers were synthesized by employing interfacial polycondensation technique and characterization of these products were carried out using standard techniques like light scattering photometer, fourier transform infrared spectroscopy (FTIR), matrix assisted laser desorption ionization time of flight mass spectroscopy (MALDI TOF MS) and nuclear magnetic resonance spectroscopy (NMR). The electrical measurements were carried out employing Genrad 1650-B impedance spectroscopy. Prior studies conducted in this area have led to the pathway of looking at two aspects; first, surveying 60 metal-containing polymers that can undergo entire chain delocalization studying the effect of different substituents on their electrical properties and secondly, doping selected candidates employing iodine. The products derived from 2-nitro-1,4-phenylenediamine and N-methyl-1,4- pheneylenediamines with titanocene dichloride exhibited about 10 3 to 10 5 fold magnitude increases in the electrical conductivity on doping with iodine, moving it near conductive region. This increase is dependent on the concentration of the iodine and is cyclic. The results support the starting premise that selected metal-containing condensation polymers can be doped to increase their electrical conductivity., Further investigation is warranted to see if metal-containing condensation polymers can be important materials in the electronic industry. This research sets the stage for studying not only metal-containing polymeric materials but also to investigate the ability to increase the conductivity of other condensation polymers such as nylons and polyesters through doping.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/216415
Subject Headings: Polycondensation, Condensation products (Chemistry), Polymers and polymerization, Polymers, Electric properties
Format: Document (PDF)

Title: Initial investigations of the magnetic circular dichroism of isobutene using synchrotron radiation in the vacuum ultraviolet region.
Creator: Sanders, Clifford., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Ethylene is the simplest alkene. The carbon-carbon double bond is ubiquitous in the field of chemistry. Ethylene serves as the basis for understanding these molecules. Thus, the assignment of the electronic transitions in ethylene is an important endeavor that many scientists have undertaken, but are yet to decipher theoretically or experimentally. Synchrotron Radiation in the vacuum ultraviolet region allows for magnetic circular dichroism (MCD) measurements of ethylene and other simple...
Show moreEthylene is the simplest alkene. The carbon-carbon double bond is ubiquitous in the field of chemistry. Ethylene serves as the basis for understanding these molecules. Thus, the assignment of the electronic transitions in ethylene is an important endeavor that many scientists have undertaken, but are yet to decipher theoretically or experimentally. Synchrotron Radiation in the vacuum ultraviolet region allows for magnetic circular dichroism (MCD) measurements of ethylene and other simple alkenes. Studies of ethylene and propylene revealed that the páap* (AgáaB1u ethylene notation) transition is not the lowest energy transition. The páa3s(R) (AgáaB3u ethylene notation) is the lowest energy transition. To further this investigation, MCD and absorption measurement were carried out on isobutene. The isobutene spectra clearly showed four electronic transitions in the 156 to 212 nm wavelength region. These four isobutene transitions have been assigned as páa3s, páap*, páa3p(Sv (Band páa3px proceeding from lower energy to higher energy. The present results support the assignments in ethylene and propylene.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/228772
Subject Headings: Bioactive compounds, Testing, Magnetic circular dichroism, Molecular spectroscopy, Spectrum analysis, Quantum theory
Format: Document (PDF)

Title: Immunoassay test strip for Microcystin-LR detection.
Creator: Xu, Jiesi., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Microcystin-LR (MCLR) is hepatotoxic to animals and humans with disruption of liver structure causing cytoskeletal damage, necrosis and pooling of blood in the liver, leading to large increase in liver weight. It is also a strong liver tumor promoter and protein phosphatase inhibitor. Microcysin-LR binds protein phosphatases 1 and 2A, and influences regulation of cellular protein phosphorylation. In the present study, a colloidal gold based immunoassay test strip was developed for Microcystin...
Show moreMicrocystin-LR (MCLR) is hepatotoxic to animals and humans with disruption of liver structure causing cytoskeletal damage, necrosis and pooling of blood in the liver, leading to large increase in liver weight. It is also a strong liver tumor promoter and protein phosphatase inhibitor. Microcysin-LR binds protein phosphatases 1 and 2A, and influences regulation of cellular protein phosphorylation. In the present study, a colloidal gold based immunoassay test strip was developed for Microcystin-LR detection. The detection limit was found to be 1 ng/mL. 5 nm colloidal gold test strips exhibits more efficient for detection, compared with 20 nm colloidal gold test strips. The interaction between Microcystin-LR antibody (immunoglobulin G) and colloidal gold nanoparticles was investigated by various analytical methods, including Ultraviolet/Visible (UV/VIS), Fourier Transform Infrared (FTIR) and Fluorescence spectroscopy as well as transmission electron microscopy (TEM).
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2683532
Subject Headings: Immunoassay, Biosensors, Environmental chemistry, Cyanobacterial toxins, Drinking water, Microbiology
Format: Document (PDF)

Title: Discovery and structural characterization of conotoxins from the venom of vermivorous cone snails.
Creator: Dovell, Sanaz., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cone snails are venomous marine gastropods that produce venom rich in neuroactive peptides, called conopeptides. The majority of published work on conopeptides has been from fish-hunting and mollusk-hunting cone snails. The work in this dissertation focuses on the discovery and characterization of novel conopeptides from the venom of worm-hunting cone snails. Eleven novel conopeptides have been isolated and biochemically characterized from the venom of C. nux using high performance liquid...
Show moreCone snails are venomous marine gastropods that produce venom rich in neuroactive peptides, called conopeptides. The majority of published work on conopeptides has been from fish-hunting and mollusk-hunting cone snails. The work in this dissertation focuses on the discovery and characterization of novel conopeptides from the venom of worm-hunting cone snails. Eleven novel conopeptides have been isolated and biochemically characterized from the venom of C. nux using high performance liquid chromatography for the isolation and purification, and mass spectrometry and nuclear magnetic resonance (NMR) spectroscopy were used for the biochemical characterization of the conopeptides. Nano-NMR spectroscopy was used as a tool to elucidate the three-dimensional structures of four conotoxins using native quantities of peptide isolated from the venom of C. nux, C. villepinii, and C. regius. In addition, the sequence-specific assignments and molecular model of a conotoxin from the venom of C. flo ridanus was also completed. The first chapter reviews the known conotoxin three-dimensional structures and cystine-constrained frameworks. The second chapter presents the mini-M conotoxins isolated from the venom of C. nux. The third chapter presents the three-dimensional NMR solution structure of a mini-M conotoxin from the venom of C. regius. The fourth chapter presents the cysteine-free conopeptides isolated from the venom of C. nux; conorfamide-nux1, a RFamide-related peptide, and nux770, a short pentapeptide. The fifth chapter presents the T-superfamily conotoxins isolated from the venom of C. nux, as well as the three-dimensional solution structure of one of the T-superfamily conotoxins. The sixth chapter presents the NMR solution structure of the first conotoxin with a cysteine-stabilized helix-loop-helix fold., Finally, the seventh chapter presents the O-superfamily conotoxins isolated from the venom of C. nux, as well as the three-dimensional solution structure of one of the O- superfamily conotoxins with an unusually knotted fold. This work shows the vast structural diversity of peptides that cone snails continue to engineer.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2684305
Subject Headings: Gastropoda, Venom, Peptides, Structure, Conus, Venom
Format: Document (PDF)

Title: Effect of external pH on cyanobacterial pigment expression.
Creator: West, Maria., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cyanobacteria are classified as alkalophiles despite their preferential uptake of the acidic form of dissolved inorganic carbon. Long term impacts of external pH on the expression of photosynthetic and structural pigments in Schizothrix calcicola were investigated as potential contributing factors to this phenomenon. More robust cell walls in S. calcicola at pH
Show moreCyanobacteria are classified as alkalophiles despite their preferential uptake of the acidic form of dissolved inorganic carbon. Long term impacts of external pH on the expression of photosynthetic and structural pigments in Schizothrix calcicola were investigated as potential contributing factors to this phenomenon. More robust cell walls in S. calcicola at pH <7 are suggested by significantly greater expression of myxoxanthophylls. Direct and indirect physiological costs of altering cell walls may contribute to S. calcicola's depressed growth at acidic pH. Comparison of chlorophylls expression suggests that alkaline rather than neutral external pH is only beneficial for S. calcicola growth in absence of nutrient limitation. While the cyanobacterial biomarker ratio of chlorophylls to echinenone was stable across the pertinent pH range of 6-8, other pigment ratios in S. calcicola were affected by pH with an approximately two week lag between the change of pH and the corresponding change of pigment expression.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2795335
Subject Headings: Environmental toxicology, Cyanobacteria, Environmental aspects, Ecosystem management, Vegetation dynamics
Format: Document (PDF)

Title: Isolation and structure elucidation of novel compounds from marine cyanobacteria.
Creator: Meickle, Theresa, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The work of this dissertation examined the secondary metabolites of several blooms of the marine cyanobacterium Lyngbya collected in Guam and Florida with an emphasis on the isolation and structure elucidation of novel biologically active compounds. The introduction in Chapter One provides a brief history of marine natural products, a description of cyanobacteria and a summary of peptides isolated from Lyngbya collected in the Caribbean. In Chapter Two, a bioassay-guided fractionation of a...
Show moreThe work of this dissertation examined the secondary metabolites of several blooms of the marine cyanobacterium Lyngbya collected in Guam and Florida with an emphasis on the isolation and structure elucidation of novel biologically active compounds. The introduction in Chapter One provides a brief history of marine natural products, a description of cyanobacteria and a summary of peptides isolated from Lyngbya collected in the Caribbean. In Chapter Two, a bioassay-guided fractionation of a Floridian collection of Lyngbya polychroa led to the isolation and structural determination of the cytotoxin desacetylmicrocolin B and the known compounds microcolins A and B. The structures were established by nuclear magnetic resonance (NMR) spectroscopic analysis. All three compounds inhibited the growth of cancer cell lines HT-29 and IMR-32 at nanomolar concentrations. Microcolins A and B were found to have little activity in the ecological assay against the marine fungus Dendryphiella salina. Chapter Three describes the isolation and structure elucidation of the glycosidic, acyl proline derivative tumonoic acid J from a sample Lyngbya sp. collected in Guam. The planar structure was determined by 1D and 2D NMR spectroscopy in conjunction with high resolution-mass spectrometry (HR-MS) data. Tumonoic acid J showed moderate activity in the ecological assay against the marine fungus D. salina. In Chapter Four, NMR-guided fractionation of a Floridian sample of Lyngbya majuscula led to the isolation of two novel cyclic peptides porpoisamides A and B. The planar structures were determined by 1D and 2D NMR spectroscopy with HR-MS data. The absolute configurations of these two compounds were defined through chiral chromatographic methods and derivatization techniques., The porpoisamides showed only moderate activity in cytotoxicity assays against cancer cell lines HCT-116 and U2OS. Finally, Chapter Five examines a potential ecological role of compounds isolated from marine cyanobacte ria. These secondary metabolites may function as chemical defenses against competing microorganisms within marine environments. Compounds isolated from cyanobacteria were tested for anti-fungal activity against the saprophytic marine fungus D. salina. Three of the six compounds tested produced inhibitory activity at or below their natural concentration.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/2978991
Subject Headings: Sponges, Ecology, Cyanobacteria, Biological control, Aquatic ecology
Format: Document (PDF)

Title: An ecological study of photoautotrophs in Lake Worth.
Creator: Bolter, Keren P., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Little Lake Worth (LLW) (800 m x 200 m x 8« m) is an artificially deep, monomictic marine basin. Pigments and other water quality parameters (O2, pH, T, S, NO3 -. etc.) were utilized to characterize phototrophic communities and water quality. The water column is dominated by diatoms except in the hypolimnon during stratification events (late Summer) when strong anoxia and H2S favors abundant Chlorobium sulfur bacteria. Results indicate nitrate-enriched freshwater baseflow indicative of septic...
Show moreLittle Lake Worth (LLW) (800 m x 200 m x 8« m) is an artificially deep, monomictic marine basin. Pigments and other water quality parameters (O2, pH, T, S, NO3 -. etc.) were utilized to characterize phototrophic communities and water quality. The water column is dominated by diatoms except in the hypolimnon during stratification events (late Summer) when strong anoxia and H2S favors abundant Chlorobium sulfur bacteria. Results indicate nitrate-enriched freshwater baseflow indicative of septic tank seepage during the wet season. This also appears to lead to the accumulation of concentrated organic matter in the sediment. LLW is a potential threat to the health of the ecosystem and the humans using it recreationally. More research is required to verify the effectiveness of restoration options. The spatial and temporal distribution of Chlorobium (phaeovibiroides tent.) and their Bacteriochlorophyll-e homologues is described and compared to similar studies.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/3151675
Subject Headings: Algae culture, Water quality, Biotic communities, Marine sediments
Format: Document (PDF)

Title: Development of Nucleophile Assisting Leaving Groups (NALGs) and new stereoselective reactions using titanium(IV) reagents.
Creator: Mondal, Deboprosad., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: We report here the development of very efficient sulfonate based leaving groups, termed Nucleophile Assisting Leaving Groups (NALGs), to accelerate the rate of nucleophilic substitution reactions involving poor nucleophiles and/or substrates traditionally considered too hindered to undergo nucleophilic attack. Indeed NALGs have shown exceptional ability in improving rate of nucleophilic substitution reactions. New very mild stereoretentive halogenations and azidation reactions have also been...
Show moreWe report here the development of very efficient sulfonate based leaving groups, termed Nucleophile Assisting Leaving Groups (NALGs), to accelerate the rate of nucleophilic substitution reactions involving poor nucleophiles and/or substrates traditionally considered too hindered to undergo nucleophilic attack. Indeed NALGs have shown exceptional ability in improving rate of nucleophilic substitution reactions. New very mild stereoretentive halogenations and azidation reactions have also been developed for secondary cyclic alcohols using NALGs involving titanium(IV) reagents. This reaction is particularly significant since the carbon-halogen bond is found widely in natural products and is used extensively as a synthesis intermediate. Azide is also a synthetically important functional group from which a variety of biologically important functional groups are conveniently obtained. Though stereoretentive chlorination and bromination reactions are known, we have developed, for the first time, a stereoretentive azidation reaction using titanium(IV) azide, a reagent not previously used in organic synthesis. During our development of stereoretentive reactions, we eventually developed very efficient, mild, two-step one-pot stereoretentive halogenations (chlorination and bromination) using titanium(IV) halides as catalysts or stoichiometric reagents. These reactions were found to be particularly efficient for cyclic alcohols. An efficient one pot stereoretentive amidation reaction for secondary cyclic alcohols is also reported. The important features of this reaction are that, for the first time, chlorosulfite (prepared in situ from alcohol using thionylchloride) has been used as a leaving group and titanium(IV) fluoride as an activator., Utilization of those two reagents is unique as thionylchloride has never been used for nucleophilic substitution reactions except in chlorination procedures. In addition, this work has found new and creative applications for titanium (IV) fluoride, a reactant rarely used in organic synthesis. Further exploiting the unique reactivity of titanium(IV), reactions of alkenes with various nucleophiles have been developed with this reagent in both catalytic and stoichiometric quantities. It was observed that a-substituted aromatic conjugated alkenes dimerize to generate important indan class of compounds which are very important in the polymer industry. In addition, non conjugated unactivated alkenes react with various nucleophiles to yield the adduct.
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Date Issued: 2010
PURL: http://purl.flvc.org/FAU/3159264
Subject Headings: Chemical reaction, Condition and laws of, Organic compounds, Synthesis, Chemical templates, Intermediates (Chemistry), Organotransition metal compounds, Organic reaction mechanisms
Format: Document (PDF)

Title: Development and applications of nucleophile assisting leaving groups (NALGs) with Titanium (IV) and Grignard reagents.
Creator: Li, Songye., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: We report here the development of very efficient aryl- and quinolinyl- sulfonate based leaving groups, termed Nucleophile Assisting Leaving Groups (NALGs), which substantially accelerate the rate of nucleophilic substitution reactions with metal halides. Detailed synthesis and kinetics study are described herein. Our synthesized NALGs have shown great reactivity towards poor nucleophiles and/or substrates traditionally considered too hindered to undergo nucleophilic attack. The abundant...
Show moreWe report here the development of very efficient aryl- and quinolinyl- sulfonate based leaving groups, termed Nucleophile Assisting Leaving Groups (NALGs), which substantially accelerate the rate of nucleophilic substitution reactions with metal halides. Detailed synthesis and kinetics study are described herein. Our synthesized NALGs have shown great reactivity towards poor nucleophiles and/or substrates traditionally considered too hindered to undergo nucleophilic attack. The abundant existence of halide, azide and amine in natural products demands new synthetic pathway. To fulfill this requirement, new mild stereoretentive halogenations (chlorination, bromination and iodination) reactions have also been developed for secondary cyclic alcohols using NALGs involving titanium (IV) reagents. The novel methodology can be extended to Azidation reactions as well with titanium (IV) azide, in which Ti (N3)4 is the first time being engaged in organic synthesis. Beased on the NALGs theory we discover the chlorosulfite can be a simplest NALG and applied as the intermediate in mild one-pot stereoretentive halogenations (chlorination and bromination) using titanium (IV) halides as catalysts or stoichiometric reagents. These reactions were found to be particularly efficient for cyclic alcohols. Finally, an efficient mild bromination and iodination reaction for primary and secondary alcohols with Grignard reagents is also reported. This reaction exhibits the generality with substrates with various leaving groups. The important features of this reaction are that, for the first time, bromide formation using Grignard reagents without the Cu (I) catalysts.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3183130
Subject Headings: Chemical kinetics, Chemical reaction, Condition and laws of, Organic compounds, Synthesis, Organotransition metal compounds, Intermediates (Chemistry), Organic reaction mechanisms
Format: Document (PDF)

Title: Purification and characterization of two members of the protein tyrosine phosphatase family: dual specificity phosphatase PVP and low molecular weight phosphatase WZB.
Creator: Livingston, Paula A., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Two protein tyrosine phosphatases, dual specificity phosphatase PVP and low molecular weight phosphatase WZB were purified and characterized. PVP was expressed as inclusion bodies and a suitable purification and refolding method was devised. Enzyme kinetics revealed that p-nitrophenylphosphate and (Sb(B-naphthyl phosphate were substrates with KM of 4.0mM and 8.1mM respectively. PVP showed no reactivity towards phosphoserine. Kinetic characterization of WZB showed that only...
Show moreTwo protein tyrosine phosphatases, dual specificity phosphatase PVP and low molecular weight phosphatase WZB were purified and characterized. PVP was expressed as inclusion bodies and a suitable purification and refolding method was devised. Enzyme kinetics revealed that p-nitrophenylphosphate and (Sb(B-naphthyl phosphate were substrates with KM of 4.0mM and 8.1mM respectively. PVP showed no reactivity towards phosphoserine. Kinetic characterization of WZB showed that only pnitrophenylphosphate was a substrate with no affinity for Ç-naphthyl phosphate and phosphoserine. Optimal conditions for activity with PNPP were found at a pH of 5 with a KM of 1.1mM, kcat of 35.4s-1 and kcat/KM of 32.2s-1mM-1. Inhibition studies showed that phosphate, fluoride, and molybdate were competitive inhibitors with Ki of 3.2mM, 71.7mM, and 50.4(So(BM respectively and hydrogen peroxide abolished activity. Active site mutants of WZB Cys9Ser and Asp115Asn showed no activity.
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Date Issued: 2009
PURL: http://purl.flvc.org/FAU/332911
Subject Headings: Protein-tyrosine phosphatase, Cellular signal transduction, Cell cycle, Regulation, Membrane proteins, Structure-activity relationships, Protein kinases
Format: Document (PDF)

Title: Light intensity influences on algal pigments, proteins and carbohydrates: implications for pigment-based chemotaxonomy.
Creator: Grant, Cidya S., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Phytoplankton Chlorophyll a (CHLa), total protein, colloidal carbohydrates, storage carbohydrates and taxonomic pigment relationships were studied in two cyanophytes (Microcystis aeruginosa and Synnechococcus elongatus), two chlorophytes (Dunaliella tertiolecta and Scenedesmus quadricauda), one cryptophyte (Rhodomonas salina), two diatoms (Cyclotella meneghiniana and Thalassiosira weissflogii) and one dinophyte (Amphidinium carterae) to assess if algal biomass could be expressed in other...
Show morePhytoplankton Chlorophyll a (CHLa), total protein, colloidal carbohydrates, storage carbohydrates and taxonomic pigment relationships were studied in two cyanophytes (Microcystis aeruginosa and Synnechococcus elongatus), two chlorophytes (Dunaliella tertiolecta and Scenedesmus quadricauda), one cryptophyte (Rhodomonas salina), two diatoms (Cyclotella meneghiniana and Thalassiosira weissflogii) and one dinophyte (Amphidinium carterae) to assess if algal biomass could be expressed in other indices than just chlorophyll a alone. Protein and carbohydrates are more useful currencies for expressing algal biomass, with respect to energy flow amongst trophic levels. These phytoplankton were grown at low light (LL = 37 (So(Bmol photons m-2 s-1), medium light (ML = 70-75 (So(Bmol photons m-2 s-1), and high light (HL= 200 (So(Bmol photons m-2 s-1)., Even though pigment per cell increased with increasing light intensity, statistically light had very little effect on the CHL a : taxonomic marker pigment ratios, as they covaried in the same way. Protein, colloidal carbohydrates and storage carbohydrates per cell all increased with increasing light intensity, but they did not covary with CHLa. Statistical data showed that light intensity had a more noticeable effect on protein: CHL a, colloidal carbohydrate: CHLa, storage CHO: CHLa, therefore a general mathematical expression for these relationships cannot be generated. This study showed that light intensity does have an influence on these biomass indices, therefore, seasonal and latitudinal formulas may be required for meaningful algal biomass estimation. However, more studies are needed if that goal is to be realized., While studying the effects of light intensity on algal pigment content and concentration, a new pigment was isolated from a cyanophyte (Scytonema hofmanii) growing between 300-1800 (So(Bmol photons¨m-2¨s-1 and from samples collected in areas of the Florida Everglades. This pigment was characterized and structurally determined to possess indolic and phenolic subunits that are characteristic of scytonemin and its derivatives. In addition, the pigment has a ketamine functionality which gives it its unique polarity and spectral properties. Based on the ultra violet/visible absorbance data, this pigment was postulated to be protecting the chlorophyll a and cytochrome Soret bands as well as a and (Sb (Bbands of the cytochromes (e.g. cytc-562) in the photosynthetic unit.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3332257
Subject Headings: Plant pigments, Analysis, Photosynthetic pgiments, Analysis, Plant allometry, Enviornmental geochemistry, Marine algae, Analysis
Format: Document (PDF)

Title: Synthesis and new reactions of allenyl carbonyls: studies towards the total synthesis of anti-thrombotic natural products Vitisinol D and C.
Creator: Maity, Pradip., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: We report here the development of new and more general synthetic pathways for the preparation of allenyl and alkynyl carbonyls. These highly dense functionalized compounds were utilized as key intermediates for the synthesis of [3.2.1] and [3.3.1] bicyclic framework, the motifs found in many natural products. A convenient method described for the dehydration of ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method...
Show moreWe report here the development of new and more general synthetic pathways for the preparation of allenyl and alkynyl carbonyls. These highly dense functionalized compounds were utilized as key intermediates for the synthesis of [3.2.1] and [3.3.1] bicyclic framework, the motifs found in many natural products. A convenient method described for the dehydration of ketoesters to generate conjugated and deconjugated alkynyl esters and conjugated allenyl esters. This sequential one-pot method involves the formation of a vinyl triflate monoanion intermediate that leads to the selective formation of alkynes or allenes depending on additives and conditions used. Product outcomes appear to be a function of unique monoand dianion mechanisms which are described. Our design of a Morita-Baylis-Hilman (MBH) reaction to include a fast silyl 1,3- Brook rearrangement has enabled the first ever anion-catalysis. This new reaction makes possible the addition of both aliphatic and aromatic aldehydes to s ilylallenes leading to carbinol allenoates. These new MBH reactions products allow for a fasttracked synthesis of [3.2.1] bisoxa-bicycles which make up the framework of many biologically active natural products including Vitisinol D. The development of cyclic addition of hydrazine nitrogen to unactivated alkynes catalyzed by non-metals is reported. Starting from readily accessible silyl allenyl esters, alkynyl hydrazines are prepared in one step and subsequently undergo unprecedented cyclization reactions in the presence of ammonium and phosphonium catalysts leading to dehydro-azaproline products. These heterocycles were also produced in high enantiomeric excesses using chiral ammonium phase transfer catalysts via a kinetic resolution pathway., The racemic synthesis of fully functionalized bicyclic core of Vitisinol D was achieved using allenyl ester as a key intermediate. The required electron withdrawing group (EWG) at the position was screened for better addition followed by the compatibility towards successive transformation and, finally, the ease of removal. A reductive aldol method to transform lactone-enol to the desired [3.2.1] bicycle was extensively studied to understand the stereoelectronic requirements for the formation of such bicyclic structures. Due to the necessity of selective protection and deprotection of many phenolic and aliphatic hydroxyls as well as ester groups, orthogonal protecting groups were established accordingly.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3332717
Subject Headings: Organic compounds, Synthesis, Carbonyl compounds, Synthesis, Cardiovascular system, Diseases, Treatment
Format: Document (PDF)

Title: Molecular characterization of the injected venom of Conus ermineus.
Creator: Rivera-Ortiz, Jose A., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cone snails are predatory marine animals that rely on their venom components to immobilize and capture their prey. According to the type of prey preference, cone snails can be divided into three groups: vermivorous, molluscivorous and piscivorous. Conus ermineus had been identified as the only piscivorous snail of the Atlantic Ocean. Cone snail venom is a complex and rich sources of natural toxins. The majority of the components of the venom are peptidic in nature, and they act over different...
Show moreCone snails are predatory marine animals that rely on their venom components to immobilize and capture their prey. According to the type of prey preference, cone snails can be divided into three groups: vermivorous, molluscivorous and piscivorous. Conus ermineus had been identified as the only piscivorous snail of the Atlantic Ocean. Cone snail venom is a complex and rich sources of natural toxins. The majority of the components of the venom are peptidic in nature, and they act over different ionic channels and membrane receptors. Initial studies using mixture of venom collected from dissected venom ducts concluded that the venom from the same species do not exhibit unusual peptide polymorphism [Olivera, Hillyard, et al., 1995] and that the only major difference between individuals of the same species are different concentrations of the venom components [Vianna, et al., 2005]. For this study, peptides in the injected venom were collected from individual snails and characterized usin g analytical RP-HPLC for a maximum of three years. The different fractions collected were processed through capillary HPLC coupled with Q-TOF ESI-MS, and compared with analytical RP-HPLC fractions processed with MALDI-TOF MS. This study demonstrates that there is an animal-to-animal variation in the peptide components of the injected venom. The injected venom remains relatively constant over time for specific specimens in captivity. Finally, there are some peptides that had been found in all specimens both by MALDI-TOF MS and by ESI-MS. In this study, these peptides are called "molecular fingerprint" peptides. Based on matches of their derived masses to those predicted by published cDNA sequences, nine novel peptides were putatively identified. This study establishes that variations due to enzymatic posttranslational modification are omitted when we consider only information extrapolated from cDNA., The results of this study support the idea of the existence of a novel regulatory mechaism to expressed specific venom peptides for injection into the prey.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3333310
Subject Headings: Gastropoda, Venom, Peptides, Structure, Coastal ecology
Format: Document (PDF)

Title: Isolation and characterization of novel conopeptides from the marine cone snail: Conus brunneus.
Creator: Pflueger, Fred C., Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cone snails are predatory marine gastropods that use venom for means of predation and defense. This venom is a complex mixture of conopeptides that selectivity binds to ion channels and receptors, giving them a wide range of potential pharmaceutical applications. Conus brunneus is a wide spread Eastern Pacific cone snail species that preys upon worms (vermivorous). Vermivorous cone snails have developed very specific biochemical strategies for the immobilization of their prey and their venom...
Show moreCone snails are predatory marine gastropods that use venom for means of predation and defense. This venom is a complex mixture of conopeptides that selectivity binds to ion channels and receptors, giving them a wide range of potential pharmaceutical applications. Conus brunneus is a wide spread Eastern Pacific cone snail species that preys upon worms (vermivorous). Vermivorous cone snails have developed very specific biochemical strategies for the immobilization of their prey and their venom has not been extensively studied to date. The main objective of this dissertation is the characterization of novel conopeptides isolated from Conus brunneus. Chapter 1 is an introduction and background on cone snails and conopeptides. Chapter 2 details the isolation and characterization of a novel P-superfamily conotoxin. Chapter 3 presents the 3D solution structure of the novel P-superfamily conotoxin. Chapter 4 details the isolation and characterization of two novel M-superfamily conotoxins. Chapter 5 covers the use of nano-NMR to characterize a novel P-superfamily conotoxin using nanomole quantities of sample. Chapter 6 is a reprint of a paper published in the Journal of the American Chemical Society in which we combined and implemented techniques developed in the previous chapters to report the presence of D-(Sd(B-Hydroxyvaline in a polypeptide chain. This dissertation contains the first reported work of a P-superfamily structure obtained directly from the crude venom therefore accurately representing native post-translational modifications. In this paper, crude cone snail venom was characterized by: high performance liquid chromatography, nuclear magnetic resonance spectroscopy, nanonuclear magnetic resonance spectroscopy, mass spectrometry, amino acid analysis, Edman degradation sequencing, and preliminary bioassays.
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Date Issued: 2008
PURL: http://purl.flvc.org/FAU/3337185
Subject Headings: Gastropoda, Venom, Peptides, Structure, Conus, Venom
Format: Document (PDF)

Title: Study of cell penetrating peptides with Raman spectroscopy and microscopy.
Creator: Ye, Jing., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cell penetrating peptides (CPPs) have drawn the attention of researchers due to their ability to internalize large cargos into cells including cancer cells. The mechanism(s) with which the peptides enter the cell, however, is/are not clear and full of controversy. The peptide conformations and their microenvironment in live cells had been unknown until the development of a technique developed in our lab. As a first demonstration of principle, penetratin, a 16-residue CPP derived from the...
Show moreCell penetrating peptides (CPPs) have drawn the attention of researchers due to their ability to internalize large cargos into cells including cancer cells. The mechanism(s) with which the peptides enter the cell, however, is/are not clear and full of controversy. The peptide conformations and their microenvironment in live cells had been unknown until the development of a technique developed in our lab. As a first demonstration of principle, penetratin, a 16-residue CPP derived from the Antennapedia homeodomain protein of Drosophila, was measured in single, living melanoma cells. Carbon-13 labeling of the Phe residue of penetratin was used to shift the intense aromatic ring-breathing vibrational mode from 1003 to 967 cm-1, thereby enabling the peptide to be traced in cells. Difference spectroscopy and principal components analysis (PCA) were used independently to resolve the Raman spectrum of the peptide from the background cellular Raman signals., On the basis of the position of the amide I vibrational band in the Raman spectra, the secondary structure of the peptide was found to be mainly random coil and b-strand in the cytoplasm, and possibly assembling as b-sheets in the nucleus. Next, label-free transportan was studied with the same methodology. The peptide, besides predominantly a-helix, adopted a significant portion of b-sheet conformation in the cytoplasm and nucleolus, which is different from the peptide in aqueous solution. The peptide microenvironment was also probed through H-bonding reported by the tyrosine Fermi doublet. Transportan displayed a tendency to accumulate in the cytoplasm over time which was unlike penetratin, which concentrated in the nucleus. The relative concentration of CPPs in various locations of live melanoma cells was directly estimated from the Raman spectra using average Phe concentration in the cell as an internal standard., The rapid entry and almost uniform cellular distribution of both peptides, as well as the lack of correlation between peptide and lipid Raman signatures, indicated that the mechanism of CPP internalization under the conditions of study was probably non-endocytotic. Last, transportan and penetratin were studied using polarized Raman spectroscopy for more detailed vibrational spectroscopic information of the two peptides in water and TFE solutions. The majority of the bands in the Raman spectra of the peptides were highly polarized, consistent with the high symmetry of aromatic ring side chain vibrational bands dispersed throughout the spectra. This work has provided new insights into the structure of CPPs in live cells and in solutions.
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Date Issued: 2011
PURL: http://purl.flvc.org/FAU/3342344
Subject Headings: Peptides, Analysis, Infrared spectroscopy, Raman spectroscopy, Cellular signal transduction
Format: Document (PDF)

Title: Mechanism of neuroprotection in stroke-related models.
Creator: Pan, Chunliu., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Stroke is the third leading cause of mortality in the United States, and so far, no clinical interventions have been proved truly effective in stroke treatment. Stroke my result in hypoxia, glutamate release and oxidative stress, etc. The purpose of this dissertation study is to evaluate the neuroprotective effects of four drugs (taurine, G-CSF sulindac and DETC-MeSO) on PC12 cell line or primary cortical neuronal cell culture, and to understand the protective mechanisms underlying in three...
Show moreStroke is the third leading cause of mortality in the United States, and so far, no clinical interventions have been proved truly effective in stroke treatment. Stroke my result in hypoxia, glutamate release and oxidative stress, etc. The purpose of this dissertation study is to evaluate the neuroprotective effects of four drugs (taurine, G-CSF sulindac and DETC-MeSO) on PC12 cell line or primary cortical neuronal cell culture, and to understand the protective mechanisms underlying in three stroke-related models : hypoxia, excessive glutamtate and oxidative stress. In the first part of this dissertation, we studied the neuroprotection of taurine against oxidative stress induced by H2O2 in PC12 cells. Our results show that extracellular taurine exerts a neuroprotective function by restoring the expression of Bcl-2 and downregulation of the three Endoplasmic Reticulum (ER) stress markers : GRP78, Bim and CHOP/GADD153, suggesting that ER stress can be provoked by oxidative stress and can be suppressed by taurine. In the second part, glutamate excitotoxicity-induced ER stress was studied with dose and time as variables in primary cortical neurons. The results demonstrate that glutamate excitotoxicity leads to the activation of three ER stress pathways (PERK, ATF6 and IRE1) by initiating PERK first, ATF6 second and IRE1 pathway last. The third part of this dissertation studied the robust and beneficial protection of taurine in cortical neurons under hypoxia/reoxygenation or glutamate toxicity condition. We found that taurine suppresses the up-regulation of GRP778, Bim, caspase-12 and GADD153/CHOP induced by excessive glutamate or hypoxia/reoxygenation, suggesting that taurine may exert a protective function against hypoxia/regeneration by reducing the ER stress., Moreover, taurine can down-regulate the ratio of cleaved ATF6 and full length ATF6, and p-IRE1 expresssion, indicating that taurine inhibits the ER stress induced by hypoxia/reoxygenation or glutamate through suppressing ATF6 and IRE1 pathways. In the fourth part, the synergistic benefits of the combination of taurine and G-CSF, and the neuroprotective effects of G-CSF, sulindac or DETC-MeSO are studied in cortical neurons. Our results show that G-CSF, sulindac or DETC-MeSO can highly increase the neuron visibility by inhibiting ER stress induced by hypoxia/reoxygenation or glutamate toxicity. Furthermore, we proved that G-CSF or sulindac can significantly inhibit the activation of ATF6 or IRE1 pathway stimulated by hypoxia/reoxygenation, and DETC-MeSO can suppress the activation of both PERK and IRE1 pathways in primary neuron cultures. These findings provide promising and rational strategies for stroke therapy.
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Date Issued: 2012
PURL: http://purl.flvc.org/FAU/3352284
Subject Headings: Sulindac, Physiological effect, Taurine, Physiological effect, Cerebral ischemia, Prevention, Biochemical markers, Diagnostic use, Apoptosis, Oxidation reduction reaction
Format: Document (PDF)

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