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Title: HUMAN CALCITONIN: AN INVESTIGATION OF AMYLOID FORMATION AND INHIBITION.
Creator: Lantz, Richard, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: Human calcitonin (hCT) is a peptide hormone that is produced by the thyroid gland where it regulates blood calcium and stimulates bone formation. However, increased concentrations can cause hCT to aggregate into amyloid fibrils where they can cause cellular toxicity. In this dissertation, we investigated the role of the N-terminal intramolecular disulfide bond, the effects cholesterol derivatives, the inhibitory effects of a group of polyphenolic molecules, and membrane interactions on hCT...
Show moreHuman calcitonin (hCT) is a peptide hormone that is produced by the thyroid gland where it regulates blood calcium and stimulates bone formation. However, increased concentrations can cause hCT to aggregate into amyloid fibrils where they can cause cellular toxicity. In this dissertation, we investigated the role of the N-terminal intramolecular disulfide bond, the effects cholesterol derivatives, the inhibitory effects of a group of polyphenolic molecules, and membrane interactions on hCT amyloid formation. To better understand hCT amyloid formation, we investigated the role of the N-terminal intramolecular disulfide bond has on the aggregation kinetics of hCT. Our results demonstrated that the presence of the disulfide bond is key to the formation of the oligomeric nucleus that is needed for amyloid formation. We also investigated the role of cholesterol, cholesterol sulfate, and 3β-[N-(dimethylaminoethane)carbamoyl]-cholesterol (DC-cholesterol) in moderating hCT fibril formation. We showed that cholesterol does not significantly affect hCT fibrillization while high concentrations of cholesterol sulfate has a moderate inhibiting effect. However, DC-cholesterol strongly inhibits hCT fibril formation in a concentration-dependent manner suggesting the role of electrostatic and hydrogen bonding interactions have in moderating the interactivity between hCT and the surface of DC-cholesterol vesicles. We also probed the inhibitory effects of a group of polyphenolic molecules on hCT fibril formation. Our results showed that molecules containing vicinal hydroxyl groups on the phenyl ring effectively inhibits hCT fibril formation though a plausible covalent linkage between the oxidized polyphenol and hCT.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013514
Subject Headings: Calcitonin, Amyloid
Format: Document (PDF)

Title: Identification of the diterpene cyclase and elucidation of early steps in the pseudopterosin biosynthetic pathway.
Creator: Kohl, Amber Celeste, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The pseudopterosins and seco-pseudopterosins are diterpene glycosides isolated from the marine soft coral, Pseudopterogorgia elisabethae . These compounds exhibit anti-inflammatory and analgesic activity greater than the industry standard, indomethacin. The overall goal of this research was to complete biosynthetic studies and enzymology related to the development of a biotechnological production method of the pseudopterosins and seco-pseudopterosins. We aimed to examine early steps in the...
Show moreThe pseudopterosins and seco-pseudopterosins are diterpene glycosides isolated from the marine soft coral, Pseudopterogorgia elisabethae . These compounds exhibit anti-inflammatory and analgesic activity greater than the industry standard, indomethacin. The overall goal of this research was to complete biosynthetic studies and enzymology related to the development of a biotechnological production method of the pseudopterosins and seco-pseudopterosins. We aimed to examine early steps in the biosynthetic pathway in order to gain detailed knowledge of the biosynthesis and enzymology of the system. Prior to examination of the biosynthetic pathway leading to the pseudopterosins, we developed both in vivo and in vitro systems to test putative precursors and demonstrated that pseudopterosin A is a precursor to pseudopterosins B--D. We also identified and confirmed the intermediacy of the pseudopterosin diterpene cyclase product using a radioactivity-guided isolation. The bicyclic structure of the diterpene cyclase product suggests that the pseudopterosins and seco-pseudopterosins are derived from this common bicyclic intermediate. The isolation of the pseudopterosin diterpene cyclase product provided us with an assay for the purification of the enzyme involved in its production. We identified the diterpene cyclase in aqueous extracts of P. elisabethae and plan to utilize the amino acid sequence for identification of the gene. This represents the first isolation of a biosynthetic enzyme from a marine coral. Moreover, various characterization studies indicated that the enzyme displays certain similar characteristics to other terpenoid cyclases isolated from terrestrial sources. In previous investigations, P. elisabethae was found only in the Bahamian and West Indian region, but we discovered P. elisabethae in the Florida Keys. Furthermore, due to the distinctive chemistry in the Florida Keys P. elisabethae, plausible early biosynthetic intermediates were isolated that are not present in the Bahamian population. We evaluated these compounds as intermediates in the biosynthesis of the pseudopterosins. The data obtained further supports the assumption of a common biosynthetic origin of the pseudopterosins and seco-pseudopterosins.
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Date Issued: 2003
PURL: http://purl.flvc.org/fcla/dt/12026
Subject Headings: Chemistry, Biochemistry, Chemistry, Organic
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: Implementation of Raman Spectroscopy into First Year Undergraduate Chemistry Curriculum.
Creator: Hyvarinen, Satu, Rezler, Evonne, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Raman spectroscopy based activities were developed and implemented into the first year chemistry undergraduate curriculum. The implementation of these experiences and experiments and the utility of Raman spectroscopy as a teaching tool to convey anchoring chemistry concepts using a hands-on Raman spectroscopy based approach are discussed. Fundamental principles of chemistry, such as the interaction of light with matter, molecular bonding, equilibrium, and acid base reactions are facilitated...
Show moreRaman spectroscopy based activities were developed and implemented into the first year chemistry undergraduate curriculum. The implementation of these experiences and experiments and the utility of Raman spectroscopy as a teaching tool to convey anchoring chemistry concepts using a hands-on Raman spectroscopy based approach are discussed. Fundamental principles of chemistry, such as the interaction of light with matter, molecular bonding, equilibrium, and acid base reactions are facilitated through use of these Raman spectroscopy based experiments and experiences. An assessment of student learning gains as a result of participation in a Raman spectroscopy experience was also conducted and is discussed.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00013017
Subject Headings: Raman spectroscopy, Undergraduate chemistry, Chemistry--Study and teaching
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: INVESTIGATING THE AMYLOIDOGENESIS OF A PRION PEPTIDE (106-128).
Creator: Regmi, Deepika, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: The misfolding of native, cellular prion protein (PrPc) to a conformationally altered pathogenic isoform, designated scrapie PrPsc, is the main molecular process involved in the pathogenesis of prion diseases. Prion diseases are marked by the accumulation of conformationally modified forms of cellular prion protein. An N-terminal portion of the prion protein, PrP (106-128), is a 23-residue peptide fragment and is characterized by an amphipathic structure with two domains: a hydrophilic N...
Show moreThe misfolding of native, cellular prion protein (PrPc) to a conformationally altered pathogenic isoform, designated scrapie PrPsc, is the main molecular process involved in the pathogenesis of prion diseases. Prion diseases are marked by the accumulation of conformationally modified forms of cellular prion protein. An N-terminal portion of the prion protein, PrP (106-128), is a 23-residue peptide fragment and is characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. In this study, the aggregation characteristics of the PrP (106-128) peptide were investigated using a combination of biophysical approaches. We investigated the effect of different factors including concentrations, pH, and metal ions, on the aggregation of the peptide. Our results demonstrated that the peptide steadily aggregates at concentrations higher than 25 M. The aggregation propensity and fibril formation is higher at pH 7.4 and pH 8.1, and the aggregation is inhibited at pH lower than 6. Furthermore, our results indicate that the Cu2+ has much less effect on the peptide amyloidogenesis, while Zn2+ has a significant influence on the PrP (106-128) amyloidogenesis. We further presented a systematic analysis of the impact of phospholipid liposomes of 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) and 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1’-racglycerol) (POPG) in the absence or presence of cholesterol, on the amyloidogenesis of PrP (106-128). The results showed that POPC vesicles does not significantly influence the aggregation kinetics of the peptide. However, the anionic lipid POPG delays the aggregation in a concentration-dependent manner, whereas the addition of POPG with the cholesterol shows fast kinetics of fibrillization, thus reducing the lag time of the aggregation kinetics. We also monitored the effect of cholesterol and its derivatives including cholesterol-SO4 and DC-cholesterol on PrP (106-128) amyloidogenesis. Our results showed that the cholesterol inhibits the peptide aggregation and delays the formation of fibrils in a concentration-dependent manner. Cholesterol-SO4 dramatically facilitates the aggregation at high concentrations but has the potential to slow down the fibrillization at low concentrations, whereas cationic DC-cholesterol vesicles can effectively inhibit peptide fibril formation at high concentrations.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013565
Subject Headings: Prion Diseases, Prions--pathogenicity, Amyloid, Peptides, Prions
Format: Document (PDF)

Title: Isocation and characterization of conotoxins from the venom of Conus Planorbis and Conus Ferrugineus.
Creator: Pak, Adriana, Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The venom of marine gastropods belonging to the genus Conus has yielded numerous structurally and functionally diverse peptidic components. The increase variety of bioactive peptides identified in cone snail venoms is the product of the variety of molecular adaptations taken by Conus species in evolving neuroactive molecules to suit their diverse biological purposes. Toxins from cone snails are classified into two major groups. One group consists of disulfide-rich peptides commonly termed...
Show moreThe venom of marine gastropods belonging to the genus Conus has yielded numerous structurally and functionally diverse peptidic components. The increase variety of bioactive peptides identified in cone snail venoms is the product of the variety of molecular adaptations taken by Conus species in evolving neuroactive molecules to suit their diverse biological purposes. Toxins from cone snails are classified into two major groups. One group consists of disulfide-rich peptides commonly termed conotoxins; the second group comprises peptides with only one disulfide bond or none. In this work, we present the discovery and characterization from the marine snails C. planorbis and C. ferrugineus. Both species are commonly found in the Indo-Pacific region and are very similar and is not distinguishable by size and shape of the shell. Novel P and T-Supefamiles were found in both species along with small linear peptides with have a high frequency of tyrosine residues. Each chapter contains a detailed look at the discovery process for the isolation and characterization of C. planorbis and C. ferrugineus. At discussion part, we also compared the peptides isolated in this work with other peptides from the literature.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004146, http://purl.flvc.org/fau/fd/FA00004146
Subject Headings: Conus, Gastropoda -- Venom, Peptides -- Structure, Venum
Format: Document (PDF)

Title: Isolation and Biomimetic Synthesis of Marine Natural Products from the Gorgonian Briareum Asbestinum.
Creator: Simpson, Johnathon, West, Lyndon M., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: Throughout history, natural products have produced a plethora of biologically active compounds that have established applications in medicine, biology, and pharmacy. The exploration for improved cytotoxic agents has continued to be a crucial path in natural products drug discovery. The focal point of this thesis sheds light on the biosynthetic relationship between the two distinct classes of briarane diterpenoids, the γ-lactone briarane and the briareolate esters. Additionally, this study...
Show moreThroughout history, natural products have produced a plethora of biologically active compounds that have established applications in medicine, biology, and pharmacy. The exploration for improved cytotoxic agents has continued to be a crucial path in natural products drug discovery. The focal point of this thesis sheds light on the biosynthetic relationship between the two distinct classes of briarane diterpenoids, the γ-lactone briarane and the briareolate esters. Additionally, this study elaborates on the discovery and elucidation of structurally unique secondary metabolites from the gorgonian coral Briareum asbestinum. The first chapter of this thesis provides a review of the development and discovery of diverse secondary metabolites. In addition, this chapter describes the role of natural products in drug discovery and summarizes the research progress in marine natural product chemistry in conjunction with a detailed overview of the current marine-derived pharmaceuticals.
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Date Issued: 2021
PURL: http://purl.flvc.org/fau/fd/FA00013857
Subject Headings: Marine natural products, Diterpenoids, Biomimetics, Soft corals
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: Isolation and Semi-synthesis of Marine Diterpenoids.
Creator: Scesa, Paul D., West, Lyndon, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: Natural products play a historical role in the discovery of medicine but present unique challenges for chemical isolation, identification and production. In this work we describe the identification of twenty novel diterpenoids. These were isolated by use of chromatography, and the structures determined by spectroscopic methods, primarily 1D and 2D NMR. Six of these possess unprecedented diterpenoid skeletons and two of them show significant growth inhibitory effects on cancer cell lines in...
Show moreNatural products play a historical role in the discovery of medicine but present unique challenges for chemical isolation, identification and production. In this work we describe the identification of twenty novel diterpenoids. These were isolated by use of chromatography, and the structures determined by spectroscopic methods, primarily 1D and 2D NMR. Six of these possess unprecedented diterpenoid skeletons and two of them show significant growth inhibitory effects on cancer cell lines in vitro (GI50 < 10 μM). The biomimetic semisynthesis of diterpendoids and analogues is also presented. Access to the bielschowskyane carbon skeleton by dearomatization of a furanocembranoid precursor is described. Highlights include a stereoselective alkene epoxidation, a novel kinetic furan dearomatization method, and an efficient [2+2] photochemical cycloaddition. The role of conformational steering was studied spectroscopically using VT 1H-NMR and NOESY as well as quantum chemical calculations at the DFT level of theory. We also disclose a biomimetic synthesis of providencin using a photochemical Norrish-Yang cyclization. This provided the absolute configuration by chemical correlation with the precursor bipinnatin E, the latter determined by x-ray diffraction. An unexpected, regioisomeric byproduct was observed and a possible mechanism is proposed. A biomimetic synthesis of the diterpene alkaloid aceropterine is also described, using an epoxidation-rearrangement cascade. This work led to a revised structure of aceropterine, formulated by spectroscopic methods. Finally, the isolation and structure elucidation of a novel, cyclic lipopeptide from Pseudomonas sp. is described. The compound was obtained using a unique antibiotic crowd sourcing approach and the structure determined by spectroscopic methods and advanced Marfey’s analysis.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013539
Subject Headings: Marine natural products, Diterpenoids, Biomimetics
Format: Document (PDF)

Title: Isolation and Structural Elucidation of Novel Bioactive Natural Products from Marine Organisms of the Western Atlantic Ocean.
Creator: Zhang, Long, West, Lyndon, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The aim of this dissertation was to elaborate the exploration of biologically active secondary metabolites from the marine sponge Cacospongia cf. linteiformis collected from the Bahamas and the soft coral Briareum asbestinum collected from two different sites in Florida State, Boca Raton and Dry Tortugas. In chapter one, a review on previous chemical and biological studies of the marine sponge C. cf. linteiformis and soft coral B. asbestinum is provided. Particular attention is given to...
Show moreThe aim of this dissertation was to elaborate the exploration of biologically active secondary metabolites from the marine sponge Cacospongia cf. linteiformis collected from the Bahamas and the soft coral Briareum asbestinum collected from two different sites in Florida State, Boca Raton and Dry Tortugas. In chapter one, a review on previous chemical and biological studies of the marine sponge C. cf. linteiformis and soft coral B. asbestinum is provided. Particular attention is given to spongianolides and briarellins, two important classes of compounds isolated from C. cf. linteiformis and B. asbestinum, respectively, and their structural features and diverse bioactivities. In chapter two, the isolation and relative configuration determination of four epimeric sesterterpenoids, spongianolides E & F (18c, 18d, 19c, 19d) from C. cf. linteiformis collected from the Bahamas are discussed. Thanks to chemical modification (acetylation), diastereomeric 18c&18d and 19c&19d, respectively, were able to be isolated using chromatographic techniques for the first time, and then the relative configurations of 18c, 18d, 19c, 19d were determined based on NOESY NMR experiments. The bioactivity of mixture of compounds 18c, 18d, 19c, 19d were tested and it exhibited inhibition against Schnurri-3 (a regulator of postnatal bone mass). In chapter three, the isolation and structural elucidation of four new compounds, florellins A-D (49-52), from B. asbestinum collected off the coast of Boca Raton, FL are discussed. The molecular structures of these compounds were established by spectroscopic analysis. Compounds 49-52 are the first briarellins containing an acyl group at C-13, while 49 and 50 are the first briarellins possessing acylation at C-15. Florellins A–C (49-51) were screened and found cytotoxic against three human cell lines, BT474, WM266−4 and HEK293. In chapter four, the isolation and structural elucidation of four new compounds, florellins E-H (57-60), from B. asbestinum collected in Dry Tortugas, FL are discussed. The molecular structures of these compounds were established by spectroscopic analysis. Florellins F (58) and H (60) were screened against three human cell lines, BT474, WM266−4 and HEK293, but no cytotoxicity was exhibited. In chapter five, all the experimental procedures are described, including analytical instruments, animal materials, extraction and isolation processes, spectroscopic data and protocols of bioassays.
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Date Issued: 2017
PURL: http://purl.flvc.org/fau/fd/FA00004850, http://purl.flvc.org/fau/fd/FA00004850
Subject Headings: Pharmacognosy., Natural products--Analysis., Marine pharmacology., Marine biotechnology., Marine algae--Biotechnology., Bioactive compounds.
Format: Document (PDF)

Title: Isolation and structure elucidation of new compounds from Cornus Controversa and Delphinium Chrysotrichum.
Creator: He, Yangqing, West, Lyndon, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The aim of this dissertation was to explore structurally unique secondary metabolites from herb medicinal plants Cornus controversa and Delphinium chrysotrichum. The introduction in the first chapter provides a detailed review about the research progress of chemical constitutents of the genus Cornus. In addition, its pharmacological activities were also summarized in this chapter to provide a framework for understanding the roles of medicinal herbs belong to genus Cornus as anti-diabetes...
Show moreThe aim of this dissertation was to explore structurally unique secondary metabolites from herb medicinal plants Cornus controversa and Delphinium chrysotrichum. The introduction in the first chapter provides a detailed review about the research progress of chemical constitutents of the genus Cornus. In addition, its pharmacological activities were also summarized in this chapter to provide a framework for understanding the roles of medicinal herbs belong to genus Cornus as anti-diabetes therapeutics and to deliver useful information for further research. In chapter two, seven new compounds, including one iridoid glucoside, cornoside A (59), five iridoid aglycones, cornolactones A – E (60 – 64) and one indenone glucoside, cornoside B (65), together with 10 known compounds have been isolated from the leaves of Cornus controversa. The structures of these compounds were established by interpretation of spectroscopic data. Cornolactone A (61) is the first natural cis-fused tricyclic dilactone iridoid containing both a five- and six-membered lactone ring. Cornoside B (65) is the first alkaloid isolated from the genus Cornus bearing an indole-3-lactic acid-11--D-glucopyranoside skeleton. In chapter three, we described the structure elucidation of three new diterpenoid alkaloids delphatisine D (77), chrysotrichumines A (78) and B (79), as well as 11 known compounds from the whole plants of Delphinium chrysotrichum. Delphatisine D (77) is a rare atisine-type alkaloid from genus Delphinium and is the C-15 epimer of spiramine C which bears an internal carbinolamine ether linkage (NCOC) between C-7 and C-20. Chrysotrichumine A (78) is a rare natural C19-diterpenoid alkaloid possessing a nitrone group between C-17 and C-19. In addition, their cytotoxic activity against human breast cancer cell lines of MCF-7 and MDA-MB-231 were also reported. In chapter four, the detailed extraction and isolation procedures of the new compounds, cornosides A and B, cornolactones A – E, delphatisine D, chrysotrichumine A and B, as well as of all the known compounds were described. In addition, the experimental procedures for the determination of PPARγ and LXR agonistic activities and the MTT cytotoxicity assay were listed in this chapter.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004121
Subject Headings: Medicinal plants., Delphinium., Cornus (Plants)
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: Isolation of briareolate esters from Briareum asbestinum.
Creator: Meginley, Rian J., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The gorgonian Briareum asbestinum is widely studied because it possesses highly oxygenated novel structures, many of which exhibit useful biological activities. Recently, two new briarane diterpenoids, briareolate esters J and K, together with two known briareolate esters have been isolated from a specimen of Briareum asbestinum collected off the coast of Boca Raton, Florida. The method used was a 96-well plate real-time cell electronic sensing (RT-CES) system to discover compounds that...
Show moreThe gorgonian Briareum asbestinum is widely studied because it possesses highly oxygenated novel structures, many of which exhibit useful biological activities. Recently, two new briarane diterpenoids, briareolate esters J and K, together with two known briareolate esters have been isolated from a specimen of Briareum asbestinum collected off the coast of Boca Raton, Florida. The method used was a 96-well plate real-time cell electronic sensing (RT-CES) system to discover compounds that impact human embryonic stem cell growth. The compounds were isolated using reversed phase polystyrene divinylbenzene chromatographic support HP20ss followed by normal phased HPLC using a luna silica column. The structures of the compounds were established though the interpretation of spectroscopic data. Activity testing was conducted against hESCs (BG02) with briareolate ester J showing no inhibition activity and briareolate ester K showing mild activity with an EC50 value of 25 (So(BM. These results confirm that the exact confirmation and existence of the (E,Z)-dienone is related to the activity that was observed with the previously isolated briareolate esters L and M.
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Date Issued: 2013
PURL: http://purl.flvc.org/fcla/dt/3360959
Subject Headings: Coral reef ecology, Marine organisms, Environmental aspects, Marine natural products, Bioactive compounds
Format: Document (PDF)

Title: Isolation of the fatty acid synthetase from the marine invertebrate Bugula neritina.
Creator: Koh, Francis H., Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The fatty acid synthetase (FAS) from the marine invertebrate Bugula neritina was isolated using cold ethanol precipitation followed by the sequence of G-100 and G-200 size exclusion columns. Native gel analysis indicates the isolation of the FAS and the elution volume from the G-100 column suggests the FAS to be ~282kd. One band with a molecular weight of 66 kDa appeared on the SDS gel of the G-200 sample (F17-30) that eluted at 52.5 mL. The G-200 sample that eluted at 19.2 mL (F1-6)...
Show moreThe fatty acid synthetase (FAS) from the marine invertebrate Bugula neritina was isolated using cold ethanol precipitation followed by the sequence of G-100 and G-200 size exclusion columns. Native gel analysis indicates the isolation of the FAS and the elution volume from the G-100 column suggests the FAS to be ~282kd. One band with a molecular weight of 66 kDa appeared on the SDS gel of the G-200 sample (F17-30) that eluted at 52.5 mL. The G-200 sample that eluted at 19.2 mL (F1-6) displayed two predominant bands on the SDS gel corresponding to molecular weights 66 kDa and 97 kDa. Both F1-6 and F17-30 showed FAS activity displaying de novo production of myristic and palmitic acids. From the sequence of purification starting from the cell-free extract (CFE) to the F17-30 sample, a 240 fold increase in specific activity was observed. The Type II FAS experiments showed no substantial evidence of activity, namely of the beta-Hydroxybutyryl acyl-dehydrase and the enoyl reductase enzymes.
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Date Issued: 1998
PURL: http://purl.flvc.org/fcla/dt/15546
Subject Headings: Fatty acids--Synthesis, Marine pharmacology, Bryozoa
Format: Document (PDF)

Title: Isolation, Analysis and Origin of Bioactive Diterpenes in Pseudopterogorgia acerosa.
Creator: Kate, Abhijeet S., Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Nature has served human kind m many ways, one of which is a source of medicines. Natural products from marine sources represent a relatively new area of research and have shown tremendous potential as a source of new chemical entities in drug discovery. Caribbean gorgomans corals of the genus Pseudopterogorgia have been shown to produce a variety of chemically interesting and biologically significant secondary metabolites. ln this dissertation, the Caribbean coral Pseudopterogorgia acerosa...
Show moreNature has served human kind m many ways, one of which is a source of medicines. Natural products from marine sources represent a relatively new area of research and have shown tremendous potential as a source of new chemical entities in drug discovery. Caribbean gorgomans corals of the genus Pseudopterogorgia have been shown to produce a variety of chemically interesting and biologically significant secondary metabolites. ln this dissertation, the Caribbean coral Pseudopterogorgia acerosa has been investigated for the presence of novel diterpenes and these compounds were found to belong to three different classes: pseudopteranoids, bis-pseudopteranoids and lipidyl pseudopteranes. Nine of these were new compounds. The structural elucidation of these compounds was performed using spectroscopic means such as l D and 20 NMR, and mass spectroscopy. There is growing evidence that secondary metabolites isolated from manne invertebrates may actually be produced by a bacterial symbiont. The research studies in our laboratory regarding the source of diterpenes in the selected gorgonian corals suggested a bacterial origin. The hypothesis that coral associated bacteria are the source of diterpenes in the coral P. acerosa, was evaluated using the series of experiments and evidence supported this biosynthetic origin. A study comparing the "gall" tissue and healthy coral tissue in terms of diterpene content and culturable bacterial communities showed that different groups of diterpenes were concentrated in different coral tissue types. It was also observed that the bacterial populations associated with the "gall" and healthy tissues were considerably different. Furthermore, observed specificity in antimicrobial activity of certain groups of compounds against bacteria isolated from the same coral suggested the ecological role of these compounds. This work with "gall" tissue supports the hypothesis that diseased coral tissue represents an excellent source of bioactive natural products for drug discovery. Additionaly, a simple LC-MS method was developed for the analysis of anticancer drug carmustine in plasma.
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Date Issued: 2008
PURL: http://purl.flvc.org/fau/fd/FA00000864
Subject Headings: Marine pharmacology, Coral reef ecology--Caribbean Area, Natural products--Synthesis
Format: Document (PDF)

Title: Isolation, Characterization and Synthesis of New Diterpenes from Pseudopterogorgia elisabethae.
Creator: Wan, Zhongliang, Florida Atlantic University, Kerr, Russell G., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Pseudopterogorgia elisabethae is a known source of structurally interesting bioactive metabolites. A detailed search for new, related compounds was undertaken in this study which resulted in the isolation and characterization of more than ten new diterpenes with serrulatane and ileabethane skeletons. Some of the new compounds isolated are closely related terpenes with significant biological activity and others are likely to be key biosynthetic intermediates. As a component of the development...
Show morePseudopterogorgia elisabethae is a known source of structurally interesting bioactive metabolites. A detailed search for new, related compounds was undertaken in this study which resulted in the isolation and characterization of more than ten new diterpenes with serrulatane and ileabethane skeletons. Some of the new compounds isolated are closely related terpenes with significant biological activity and others are likely to be key biosynthetic intermediates. As a component of the development of a production method of anti-inflammatory compounds such as seco-pseudopterosin and elisabethadione, a synthesis of a seco-pseudoperosin aglycone from elisabethatriene was developed.
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Date Issued: 2006
PURL: http://purl.flvc.org/fau/fd/FA00000883
Subject Headings: Biosynthesis, Diterpenes--Synthesis, Marine invertebrates, Anti-inflammatory agents
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: Manganese-promoted rearrangement of alkynyl carbonyls to allenyl carbonyls with emphasis on asymmetric induction using chiral bases.
Creator: Khoram, Anita, Florida Atlantic University, Lepore, Salvatore D., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The conversion of alkynyl carbonyls to allenyl carbonyls via manganese mediated coordinations followed by a based-catalyzed isomerization was carried out using a range of chiral and achiral amine bases. In this work we employed HPLC equipped with a chiral column to determine the enantiomeric excess. Deuterium labeling experiments suggested that the alkyne/allene rearrangement reaction involved an intermediate cumenolate. We also demonstrated that the reaction required a ligand on manganese...
Show moreThe conversion of alkynyl carbonyls to allenyl carbonyls via manganese mediated coordinations followed by a based-catalyzed isomerization was carried out using a range of chiral and achiral amine bases. In this work we employed HPLC equipped with a chiral column to determine the enantiomeric excess. Deuterium labeling experiments suggested that the alkyne/allene rearrangement reaction involved an intermediate cumenolate. We also demonstrated that the reaction required a ligand on manganese for an amine base to be used catalytically. Phosphines were tested as a possible ligand because they are neutral two electron donors that binds to transition metals through their lone pairs. It was observed that the rate of the reaction decreased from 24hr to 3hr by use of phosphine as a ligand. It was also confirmed that amine base with pKa lower then DBU (pKa = 13.6) would not carry out the isomerization. Chiral amidine and chiral DBU derivatives were synthesized to carry out the isomerization enantioselectively. Alkoxy base were also used in isomerization that demonstrated enantioselectivity.
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Date Issued: 2004
PURL: http://purl.flvc.org/fcla/dt/13158
Subject Headings: Carbonyl compounds--Synthesis, Organic compounds--Synthesis, Allene, Alkenes, Methathesis (Chemistry), Isomerism
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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