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- Title
- AMYLOIDOGENICITY OF THE PEPTIDE FRAGMENT IN MICROTUBULE BINDING REPEAT DOMAIN OF TAU.
- Creator
- Islam, Majedul, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Tau, a microtubule-associated protein, is involved in more than 20 different tauopathic disorders characterized by aberrant intracellular aggregation of tau in the brain. However, it is still unclear how this highly soluble tau protein aggregates inside the brain. Thus, understanding the mechanistic details of tau aggregation is critical for unraveling the underlying pathology of tauopathies and developing effective strategies to inhibit tau aggregation. Herein, we investigated the...
Show moreTau, a microtubule-associated protein, is involved in more than 20 different tauopathic disorders characterized by aberrant intracellular aggregation of tau in the brain. However, it is still unclear how this highly soluble tau protein aggregates inside the brain. Thus, understanding the mechanistic details of tau aggregation is critical for unraveling the underlying pathology of tauopathies and developing effective strategies to inhibit tau aggregation. Herein, we investigated the aggregation of a novel 20-residue model peptide, tau₂₉₈₋₃₁₇, derived from the key microtubule-binding domain of the full sequence tau. Our study demonstrates that tau₂₉₈₋₃₁₇ highly mimics full-length tau's physical and aggregation properties. The fibrillation of the peptide is strongly dependent on external factors. The presence of polyanionic heparin (Hep) significantly promotes the aggregation of this peptide to form amyloid fibrils. The Hep-induced aggregation is sensitive to the ionic strength of the solution, suggesting an important role of electrostatic interactions in the mechanism of Hep-mediated aggregation. In addition, two positively charged polysaccharides, chitosan (CHT) and its quaternary derivative N-trimethyl chitosan (TMC), effectively inhibit Hep-induced aggregation of tau₂₉₈₋₃₁₇ in a concentration-dependent manner. Attractive electrostatic interactions between the positively charged moieties in CHT/TMC and the negatively charged residues of Hep play a critical role in inhibiting Hep–peptide interactions and suppressing peptide aggregation.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014211
- Subject Headings
- tau Proteins, Tauopathies, Amyloidogenic Proteins
- Format
- Document (PDF)
- Title
- Crafting Attractive Non-Covalent Interactions for the Study of β-Hairpins with Long Loops.
- Creator
- Richaud, Alexis D., Roche, Stéphane P., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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In this study, we developed a new peptide motif called β-strap (strap = strand + cap) used to fold β-hairpins of varying length. β-Straps are mean to be short sequences (4 to 8 a-amino acids) forming β-sheets using a judicious combination of non-covalent interactions (NCI) to overcome the entropic penalty inherent to long loop closure. Among those, we proved that a couple of CH-π / NH-π interactions from a tryptophan zipper motif were critical to create a stable packing of the structure. To...
Show moreIn this study, we developed a new peptide motif called β-strap (strap = strand + cap) used to fold β-hairpins of varying length. β-Straps are mean to be short sequences (4 to 8 a-amino acids) forming β-sheets using a judicious combination of non-covalent interactions (NCI) to overcome the entropic penalty inherent to long loop closure. Among those, we proved that a couple of CH-π / NH-π interactions from a tryptophan zipper motif were critical to create a stable packing of the structure. To optimize these interactions, we incorporated unnatural tryptophan derivatives having functionalized indole side chains. Finally, the innate ability of the β-strap to bring β-stand in close contact was exploited to promote macrocyclization of long coiled peptides (up to 16 residues). Then, we studied a more complex β-hairpin loop mimics found at the apex of monoclonal antibodies (mAb) complementary determining region 3 (CDR-H3). Using a set of bioinformatics tools, a search of PDB crystal structures revealed that a large set of mAb crystals possess a β-bulge, located at the edge of CDR-H3 loops. A cluster analysis revealed it has an impressive adaptability towards different H3-loop sizes and conformations. In order to evaluate its function in antibodies, we synthesized several β-hairpin models bearing a prototypical β-bulge. By combining short β-straps and the β-bulge, we were able to design β-hairpin peptides mimic of mAb with a variety of lengths and rigidity while retaining a high degree of folding. Starting from pembrolizumab, the most outstanding blocker of the PD-1/PD-L1 checkpoint currently available in clinic, we scoped ~30 CDR-H3 mAb mimics (H3 loop). As a result, several novel β-hairpin peptide inhibitors of the PD-1/PD-L1 pathway were identified (IC50 <0.3 μM).
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014154
- Subject Headings
- Antibodies, Peptides, Biochemistry, β-Hairpins
- Format
- Document (PDF)
- Title
- RESVERAMORPHS AS PROTECTIVE AGENTS AGAINST EPILEPSY: OPTIMIZATION OF REDUCTIVE ALDOL BICYCLIZATION AND ANALOG SYNTHESIS WITH FUNCTIONAL GROUP VARIATION TO ASSESS IMPACT ON BIOACTIVITY.
- Creator
- Jutte, Elyse M., Lepore, Salvatore D., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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This work encompasses the synthesis, analysis, and optimization of [3.2.1] all-carbon bridged bicyclic compounds, known as resveramorphs (RVM), Studies were conducted using a Caenorhabditis elegans model, where RVMs were tested for antiseizure capabilities. In both applications, RVMs proved potent with activities in the sub-nanomolar level in one case. A structure-activity relationship (SAR) was hypothesized for the identification of the pharmacophore. The six to seven step synthesis route...
Show moreThis work encompasses the synthesis, analysis, and optimization of [3.2.1] all-carbon bridged bicyclic compounds, known as resveramorphs (RVM), Studies were conducted using a Caenorhabditis elegans model, where RVMs were tested for antiseizure capabilities. In both applications, RVMs proved potent with activities in the sub-nanomolar level in one case. A structure-activity relationship (SAR) was hypothesized for the identification of the pharmacophore. The six to seven step synthesis route towards the RVM analogues is discussed in further detail. The bicyclization of the RVMs is achieved through a reductive aldol reaction. The reaction suffers from selectivity issues leading to multiple bicyclic products. By following a one-factor-at-a-time (OFAT) methodology, attempts at optimization for this reaction were made, however, despite important gains, the overall yields of the bicyclic product remain low. Other products from this reaction have been used to understand the reaction mechanism, which will be the basis for future efforts to further optimize this key step.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014288
- Subject Headings
- Epilepsy--Animal models, Bridged Bicyclo Compounds, Resveratrol
- Format
- Document (PDF)
- Title
- Studying the Effects of Lipid Membranes and Polysaccharides on the Amyloidogenicity of Fragments of Amyloid Beta.
- Creator
- Petersen, Katherine, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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The amyloid beta (Aβ) peptide has been linked to Alzheimer’s Disease (AD) since the early 1990s. Since then, many studies have characterized the peptide and examined its aggregation process. Aβ is a 40 or 42-residue peptide, composed of a charged N-terminal and hydrophobic C-terminal, that aggregates into characteristic β-sheets forming insoluble plaques in the brains of (AD) patients. In recent years an intermediate oligomeric species has been shown to interact with lipid membranes, largely...
Show moreThe amyloid beta (Aβ) peptide has been linked to Alzheimer’s Disease (AD) since the early 1990s. Since then, many studies have characterized the peptide and examined its aggregation process. Aβ is a 40 or 42-residue peptide, composed of a charged N-terminal and hydrophobic C-terminal, that aggregates into characteristic β-sheets forming insoluble plaques in the brains of (AD) patients. In recent years an intermediate oligomeric species has been shown to interact with lipid membranes, largely resulting in the etiology of AD. In this study, two fragments are used, the 23-residue N-terminal fragment, Aβ23 and the 30-residue C-terminal fragment, Aβ11-40, to better understand the role of the N and C-terminus in the aggregation of Aβ peptide. Aβ11-40 has also been found in the brains of AD patients, playing a biological role in the disease. This study used analytical and biophysical techniques to systematically synthesize, purify, characterize, and study these fragments' aggregation in different conditions. We investigated the effects of lipid membranes on the aggregation of Aβ23 and Aβ11-40 and the activities of these peptides in inducing membrane damage. The results show that the aggregation of Aβ23 was increased in the presence of lipid membranes, likely due to favorable electrostatic interactions. However, the aggregation of Aβ11-40 was not influenced by lipid membranes. A dye leakage study was carried out to study the membrane damage occurring as a result of fragments' interaction with lipid membranes. The results showed that neither fragment had a profound effect on membrane destruction, although the charge of the lipid head seemed to play a role. This work's second study focused on the effect of three specific polysaccharides, heparin, chitosan (CHT), and trimethyl chitosan (TMC), on the aggregation of Aβ23 and Aβ11-40. The results showed that for Aβ23, heparin increased aggregation, while both CHT and TMC decreased aggregation. However, for Aβ11-40, both heparin and CHT did not affect aggregation, while TMC decreased aggregation.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014294
- Subject Headings
- Amyloid beta-Peptides, Alzheimer's disease
- Format
- Document (PDF)
- Title
- GULF STREAM INTRUSIONS AS CONDUITS FOR LARVAL FISHES ALONG FLORIDA’S EAST COAST.
- Creator
- Woodward, Caroline, Chérubin, Laurent, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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The mechanisms of larval fish transport have been rigorously studied in the past several decades, building foundational knowledge of key biological and environmental factors with which to inform decisions about species management. This study has been built upon information gained from previous studies to further elucidate the processes involved at the recruitment stage of larval fishes. Vertical swimming behaviors of larval fishes enable deliberate orientation within the water column to allow...
Show moreThe mechanisms of larval fish transport have been rigorously studied in the past several decades, building foundational knowledge of key biological and environmental factors with which to inform decisions about species management. This study has been built upon information gained from previous studies to further elucidate the processes involved at the recruitment stage of larval fishes. Vertical swimming behaviors of larval fishes enable deliberate orientation within the water column to allow organisms of limited mobility greater control over their horizontal movements. Vertical accumulation patterns of larvae are found to be tightly dependent on the strength of stratification within the water column at nursery entrances, such as estuaries. Onshore currents, such as upwelling and surface intrusions, are found to be conduits for entry into these systems. This study observed and analyzed the influence of intrusions by the Gulf Stream into the Fort Pierce Inlet and the vertical accumulation patterns of late-stage larvae associated with those events. This study incorporated a well-established zooplanktonic abundance sampling technique to achieve two primary goals: (1) to analyze the vertical abundances of larval fishes in stratified flow during Gulf Stream intrusions and (2) to assess the correlation between larval influx and intrusion events. The results of this study show a significant and positive correlation between propagule pressure of larval fishes and incidence of Gulf Stream intrusion events. Whereas previous studies have primarily described the spatiotemporal aspects of larval transport in a broader sense, our findings revealed a greater layer of complexity in the mechanisms of transport by incorporating localized hydrographic features. The information gleaned from these results can inform the ecological considerations of future fisheries management and study efforts via additional understanding about the role of physical oceanographic events in a critical life stage.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014263
- Subject Headings
- Gulf Stream (Fla.), Larvae--Dispersal, Fishes--Larvae
- Format
- Document (PDF)
- Title
- DISSECTING THE MECHANISTIC ROLES OF REGULATORS IN MEDIATING AMYLOID-BETA AMYLOIDOGENESIS.
- Creator
- Shen, Fengyun, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Alzheimer’s disease (AD) is a common neurodegenerative disorder. The most recognized disease pathology is the Amyloid-β (Aβ) cascade hypothesis which states that the accumulation of Aβ plaques might be the cause of AD. In the AD brain, Aβ plaques stockpile a variety of molecular components including metals, lipids, nucleic acids, carbohydrates, and peptides, indicating Aβ aggregation might be influenced by these modulators. In this dissertation, we investigated the effects of Zn2+ and...
Show moreAlzheimer’s disease (AD) is a common neurodegenerative disorder. The most recognized disease pathology is the Amyloid-β (Aβ) cascade hypothesis which states that the accumulation of Aβ plaques might be the cause of AD. In the AD brain, Aβ plaques stockpile a variety of molecular components including metals, lipids, nucleic acids, carbohydrates, and peptides, indicating Aβ aggregation might be influenced by these modulators. In this dissertation, we investigated the effects of Zn2+ and carnosine, phospholipids, and β-hairpins on Aβ aggregation to dissect their mechanistic roles in the amyloidogenesis of Aβ. We first systematically studied the kinetic impact of Zn2+ on the aggregation of Aβ40 and Aβ40-M. Our results show that the presence of Zn2+ transforms the Aβ40 aggregation kinetics from a single sigmoidal to a biphasic process, while the aggregation of Aβ40-M is significantly suppressed by Zn2+. We also found that a nature dipeptide, carnosine, remarkably decreases the activity of Zn2+ on modulating Aβ aggregation, although it has a weak direct effect on the peptide aggregation kinetics. Second, we investigated the activities of Aβ40 and Aβ42 in inducing membrane damage and the effects of lipid membranes on the aggregation of these peptides using liposome models containing mitochondrial-specific phospholipid–cardiolipin (CL).
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014314
- Subject Headings
- Alzheimer's disease, Amyloid beta-Peptides, Neurodegenerative Diseases
- Format
- Document (PDF)
- Title
- Synthesis and Biological Evaluation of β-hairpin Peptides as Covalent Inhibitors of the PD-1/PD-L1 Immune Checkpoint.
- Creator
- Naylon, Sarah, Roche, Stephane, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Protein─protein interactions (PPIs) are essential for cell─cell interactions and cellular signal transduction, which play a crucial role in various human diseases. PPIs involved in cancer immunology pathways, known as immune checkpoints, have been intensely studied, leading to a new approach to cancer therapy. The PD1:PDL1 interaction is one of the most essential immune checkpoints. Studies on PD1:PDL1 showed over ten clinical monoclonal antibodies (mAb) used to treat cancer patients....
Show moreProtein─protein interactions (PPIs) are essential for cell─cell interactions and cellular signal transduction, which play a crucial role in various human diseases. PPIs involved in cancer immunology pathways, known as immune checkpoints, have been intensely studied, leading to a new approach to cancer therapy. The PD1:PDL1 interaction is one of the most essential immune checkpoints. Studies on PD1:PDL1 showed over ten clinical monoclonal antibodies (mAb) used to treat cancer patients. Unfortunately, antibodies do not penetrate the tumor microenvironment well, and clearance from the body is slow, leading to unwanted side effects. There is a significant gap in the drug market between the typical Rule of 5 (Ro5) small-molecule drugs (MW<0.5 kDa, SASA ~150 Å) and large antibodies with molecular weights greater than 40 kDa (SASA >2,000 Å). PPIs remain challenging to modulate by small molecules due to their large, shallow, often dynamic, and water-exposed surfaces lacking well-defined binding pockets. Thus, our lab was drawn to work on large β-hairpin peptides (2-3 kDa) that can potentially mimic the CDR-H3 loops of some of the most potent and clinical anti-PD1 antibodies. Exploration of these β-hairpin peptides provided valuable insights into their folding stability, conformational flexibility, passive membrane permeability, and protein-protein interaction (PPI) blocking activities. Additionally, the rational design of TCIs against PD1, specifically targeting a lysine residue, emerged as a strategy to irreversibly obstruct the PD1:PDL1 protein-protein interaction enhancing potency of the non-covalent inhibitors by taking advantage of their specificity. Meticulous structural analysis, peptide synthesis, and biological evaluations are presented contributing comprehensions into covalent inhibitor development of drugs fbRo5.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014353
- Subject Headings
- Cancer--Immunological aspects, Protein-protein interactions, Antibodies, Monoclonal
- Format
- Document (PDF)
- Title
- PRION FRAGMENT 106-128: AN INVESTIGATION OF AMYLOID FORMATION AND INHIBITION.
- Creator
- Regmi, Deepika, Du, Deguo, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Misfolding and aggregation of Cellular Prion Protein (PrPc) is a major molecular process involved in the pathogenesis of Prion diseases. An N-terminal portion of the Prion protein, PrP106-128, is a 23-residue peptide fragment characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. Here, we studied the aggregation properties of the prion fragment peptide PrP106-128. The results show that the peptide aggregates in a...
Show moreMisfolding and aggregation of Cellular Prion Protein (PrPc) is a major molecular process involved in the pathogenesis of Prion diseases. An N-terminal portion of the Prion protein, PrP106-128, is a 23-residue peptide fragment characterized by an amphipathic structure with two domains: a hydrophilic N-terminal domain and a hydrophobic C-terminal domain. Here, we studied the aggregation properties of the prion fragment peptide PrP106-128. The results show that the peptide aggregates in a concentration-dependent manner in an aqueous solution and that the aggregation is sensitive to pH and the preformed amyloid seeds.Furthermore, we show that the zwitterionic POPC liposomes moderately inhibit the aggregation of PrP(106–128), whereas POPC/cholesterol (8:2) vesicles facilitate peptide aggregation likely due to the increase of the lipid packing order and membrane rigidity in the presence of cholesterol. In addition, anionic lipid vesicles of POPG and POPG/cholesterol above a certain concentration accelerate the aggregation of the peptide remarkably. The strong electrostatic interactions between the N-terminal region of the peptide and POPG may constrain the conformational plasticity of the peptide, preventing insertion of the peptide into the inner side of the membrane and thus promoting fibrillation on the membrane surface. The results suggest that the charge properties of the membrane, the composition of the liposomes, and the rigidity of lipid packing are critical in determining peptide adsorption on the membrane surface and the efficiency of the membrane in catalyzing peptide oligomeric nucleation and amyloid formation.
Show less - Date Issued
- 2023
- PURL
- http://purl.flvc.org/fau/fd/FA00014356
- Subject Headings
- Prion Proteins, Prion diseases, Epigallocatechin gallate, Amyloid
- Format
- Document (PDF)
- Title
- DIASTEREOSELECTIVE ADDITION OF H-PHOSPHINATES TO ALKENYL KETONES UNDER PHASE-TRANSFER CONDITIONS AND SYNTHESIS OF BRIDGED BICYCLIC COMPOUNDS FOR BIOLOGICAL EVALUATION.
- Creator
- Yadavalli, Krishna Prasad, Lepore, Salvatore D., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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In the present dissertation, we discuss the development of a stereoselective method for the production of phosphorus compounds that utilizes a phospha-Michael addition reaction. Separately, the design and synthesis of compounds that contain an all-carbon bridged bicyclic scaffold is reported; these compounds were used in initial SAR studies in different in vivo models. In Chapter one is presented a mechanistic framework to develop a highly diastereoselective method catalyzed by phase transfer...
Show moreIn the present dissertation, we discuss the development of a stereoselective method for the production of phosphorus compounds that utilizes a phospha-Michael addition reaction. Separately, the design and synthesis of compounds that contain an all-carbon bridged bicyclic scaffold is reported; these compounds were used in initial SAR studies in different in vivo models. In Chapter one is presented a mechanistic framework to develop a highly diastereoselective method catalyzed by phase transfer chemistry leading to phosphinate compounds. In this method, phosphinate nucleophiles were added to various alkenyl ketones as Michael acceptors using crown ethers as phase transfer agents to obtain highly diastereoselective products with the generation of a carbon-based quaternary centers. A closed transition state mechanism is proposed to describe the diastereoselectivity observed in the reactions that is consistent with product outcome as established by X-ray crystallography. Analysis using the 31P NMR technique is also reported to ascertain the diastereomeric ratios in product formation. Using products obtained with the newly developed method, we disclose for the first time a novel phospha-heterocycle with high control of stereochemistry. Relative stereochemistry of the phosphorus containing heterocycle was reported using 2D NMR analysis. In Chapter two focus is placed on the use of acrylates as Michael acceptors in both the diastereoselective and enantioselective studies of phospha-Michael addition. In the asymmetric method development, screening of various chiral catalysts and development of HPLC method to quantify the enantiopurity of products obtained under reaction conditions are reported. The role of crown ether catalysts towards diastereoselectivity is reported.
Show less - Date Issued
- 2022
- PURL
- http://purl.flvc.org/fau/fd/FA00014015
- Subject Headings
- Bridged bicyclic compounds, Chemistry, Organic, Organic compounds--Synthesis
- Format
- Document (PDF)
- Title
- MULTIVALENT PROTEIN GLYCOSYLATION: A DRIVING FORCE OF CANCER PROGRESSION AND ALZHEIMER’S DISEASE PATHOGENESIS.
- Creator
- Singh, YashoNandini, Cudic, Maré, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Glycosylation is a frequent and heterogeneous post-translational protein modification occurring in all domains of life. Aberrant cell-surface glycosylation is shown to mediate several processes involved in tumor cell proliferation, adhesion, and metastasis. Recent findings linked altered protein glycosylation to Alzheimer’s disease (AD) pathogenesis. One key obstacle in studying functional consequences of glycosylation has been the lack of structurally defined glycopeptide or protein model...
Show moreGlycosylation is a frequent and heterogeneous post-translational protein modification occurring in all domains of life. Aberrant cell-surface glycosylation is shown to mediate several processes involved in tumor cell proliferation, adhesion, and metastasis. Recent findings linked altered protein glycosylation to Alzheimer’s disease (AD) pathogenesis. One key obstacle in studying functional consequences of glycosylation has been the lack of structurally defined glycopeptide or protein model compounds for biochemical studies at the molecular level. For tumor progression, studies are crucial towards understanding the glycan-lectin recognition process tied to deciphering the information contained in glycan structures and for AD, foundational studies are necessary for understanding the role of O-glycosylation in protein processing and its fate toward the amyloid pathway. In chapter 1, a highly O-glycosylated transmembrane and cancer-associated mucin protein, MUC1, is used as a model for designing synthetic tools for exploring its role in metastasis via association with lectins and specificity of anti-MUC1 antibodies. This dissertation for the first time presents a MUC1-based positional scanning synthetic glycopeptide combinatorial library that varies in the number and location of tumor-associated Tn antigen. The importance of defined structural complexity for evaluating glycan density and glycosylation patterns for binding to Tn-specific plant lectins and anti-MUC1 (mouse) monoclonal antibodies was revealed using an enzyme-linked lectin assay (ELLA). Chapter 2 addressed the growing significance of peptide lectinomimics for recognizing tumor-specific glycans. Fluorescently labelled alanine scan analogues of odorranalectin (OL), a cyclic peptide that exhibits lectin like properties, were screened for binding BSA-conjugated monosaccharides using ELLA. Results revealed that Lys5, Phe7, Tyr9, Gly12, Leu14, and Thr17 were crucial for binding BSA-L-fucose, BSA-Dgalactose and BSA-N-acetyl-D-galactosamine. The thermodynamics of binding of the selected alanine analogues was evaluated by isothermal titration calorimetry. The thermodynamic profile of interactions with asialofetuin exhibits shift to an entropy-driven mechanism compared to fucoidan, which displayed an enthalpy-entropy compensation, typically associated with the carbohydrate-lectin recognition process. Chapter 3 focused on amyloid-precursor protein (APP) O-glycosylation and its role in AD pathogenesis. We synthesized native and Swedish-mutated (glyco)peptides with O-GalNAc moiety on Thr663 and/or Ser667 or Tyr681 to explore the role of glycosylation on conformation, secretase activity, and aggregation kinetics of Aβ40. Our results show that conformation is strongly dependent on external conditions such as buffer ions and solvent polarity as well as internal modifications of (glyco)peptides such as length, O-glycosylation, and Swedish mutation (Lys670Asn/Met671Leu). Furthermore, the level of β-secretase activity significantly increased for the glycopeptides containing the Swedish mutation compared to their nonglycosylated and native counterparts. Lastly, glycopeptides impacted the kinetics of Aβ40 aggregation by significantly increasing the lag phase and delaying aggregation onset, however, this effect was less pronounced for its Swedish-mutated counterparts.
Show less - Date Issued
- 2022
- PURL
- http://purl.flvc.org/fau/fd/FA00013949
- Subject Headings
- Glycosylation, Alzheimer Disease, Lectins
- Format
- Document (PDF)
- Title
- TUMOR-ASSOCIATED MUC1-TN GLYCOPEPTIDE INTERACTIONS WITH MACROPHAGE GALACTOSE LECTIN.
- Creator
- Beckwith, Donella Marie, Cudic, Mare, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
The transformation from normal to malignant phenotype in human cancers is associated with aberrant cell-surface glycosylation. Mucin 1 (MUC1), the heavily glycosylated cell-surface mucin, is altered in both, expression and glycosylation pattern in many cancers. The presence of truncated glycan structures, often capped by sialic acid, commonly known as tumor-associated carbohydrate antigens (TACAs), play key roles in tumor initiations, progression, and metastasis. Accumulating evidence...
Show moreThe transformation from normal to malignant phenotype in human cancers is associated with aberrant cell-surface glycosylation. Mucin 1 (MUC1), the heavily glycosylated cell-surface mucin, is altered in both, expression and glycosylation pattern in many cancers. The presence of truncated glycan structures, often capped by sialic acid, commonly known as tumor-associated carbohydrate antigens (TACAs), play key roles in tumor initiations, progression, and metastasis. Accumulating evidence suggests that expression of TACAs is associated with escape of immune defenses. Human macrophage galactose-type lectin (hMGL, HML, CD301 or CLEC10A), a C-type lectin expressed by antigen presenting cells (APC), is a receptor of mucin-type TACAs, -GalNAc (Thomsen nouvelle antigen; Tn; CD175) and its 2,6-sialylated derivative (sTn; CD175s). To date, the relative contributions of these glycans, as well as underlying peptide backbone, and different degrees of valency, on binding thermodynamics and kinetics with hMGL remains elusive. In order to discern the subtle utility of these distinct features, chemical syntheses of the MUC1, HGVTSAPDTRPAPGSTAPPA tandem repeat sequence, and its site-specific serine (Ser) and threonine (Thr) glycosylated analogs were carried out. Circular dichroism (CD) spectroscopy experiments detected increasing structural order of the Thr glycopeptides compared to its nonglycosylated analogs. Isothermal titration calorimetry (ITC) data analysis of lectin binding to the Thr glycopeptides invariably showed enthalpy-driven processes. Affinity enhancement of the Thr glycopeptides for hMGL occurred relative to free GalNAc, revealing an increasing trend in affinity by one order of magnitude, for mono- (KD = 6-8 μM) to triglycosylated (KD = 600 nM) MUC1 peptides. To delineate the relevance of the solvent structure in the protein carbohydrate recognition process, experiments in D2O were performed, exposing enthalpy-entropy compensation differences. KinITC analysis highlighted prolonged complex lifetimes. Furthermore, atomic force microscopy (AFM) based dynamic single-molecule force spectroscopy (SMFS) provided molecular level insight into the energy landscapes governing recognition of the MUC1(Tn)-hMGL complexes. In summary, our results suggest that contact with hMGL critically depends on the type of TACA, nature of the vicinity surrounding the glycan, and its density. This highlights the importance and current efforts in design of prophylactic and therapeutic cancer vaccines with special emphasis on the synthetic glycopeptide vaccines.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013750
- Subject Headings
- Antigens, Tumor-Associated, Carbohydrate, Mucin-1, Cancer vaccines, Glycopeptides
- Format
- Document (PDF)
- Title
- MECHANISTIC STUDIES OF THE PLP-DEPENDENT ENZYME, METHIONINE GAMMA-LYASE AND THE HEME-DEPENDENT ENZYME, INDOLEAMINE 2,3-DIOXYGENASE.
- Creator
- Foo, Timothy, Terentis, Andrew C., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
-
Methionine-γ-lyase (MGL) is a pyridoxal-5′-phosphate (PLP) dependent enzyme found in bacteria and protozoa that catalyzes a variety of reactions, including the γ-elimination of L-methionine (L-Met). Besides its physiological roles in organisms, MGL is also a therapeutic target for pathogenic diseases and cancer. Since MGL’s catalytic mechanism remains uncertain, a new spectrophotometric assay was validated for measuring the kinetics of MGL catalyzed reactions. Kinetic data and density...
Show moreMethionine-γ-lyase (MGL) is a pyridoxal-5′-phosphate (PLP) dependent enzyme found in bacteria and protozoa that catalyzes a variety of reactions, including the γ-elimination of L-methionine (L-Met). Besides its physiological roles in organisms, MGL is also a therapeutic target for pathogenic diseases and cancer. Since MGL’s catalytic mechanism remains uncertain, a new spectrophotometric assay was validated for measuring the kinetics of MGL catalyzed reactions. Kinetic data and density functional theory (DFT) data for the γ-elimination reaction of L-Met and several other substrate analogues by MGL from P. gingivalis is reported. A direct correlation between experimental kcat values and DFT-calculated activation energies of the γ-cleavage reaction of the enamine intermediate was identified for various substrates. Considering these data, we propose a catalytic mechanism for MGL catalysis, whereby the γ-cleavage step is rate-limiting. This conclusion has direct implications for the rational design of substrates or inhibitors aimed at regulating MGL activity. PLP-dependent enzymes are present in all organisms and account for ~4% of all discovered enzyme activities. They all possess a common external aldimine and quinonoid intermediate at the start of their reaction pathway but likely diverge thereafter into different reaction pathways based on their substrate(s) and active site environment. To yield insight into the divergent reactivity of the quinonoid intermediate, DFT calculations of several PLP-dependent enzymes with unique reactivity revealed that the charge distribution is modulated on Cα and C4’, which allows for the regioselectivity of the quinonoid intermediate. The mammalian heme enzyme indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the first reaction of L-tryptophan (L-Trp) oxidation along the kynurenine pathway. IDO1 is a central immunoregulatory enzyme with important implications for inflammation, infectious disease, autoimmune disorders, and cancer. Since IDO1’s catalytic mechanism remains uncertain, kinetic data and DFT data for the dioxygenation reaction of L-Trp and several other substrate analogues by human IDO1 is reported. A direct correlation between experimental kcat values and DFT-calculated activation energies of the C2-O cleavage reaction of the L-Trp-epoxide intermediate was identified for various substrates. This conclusion has direct implications for the rational design of substrates or inhibitors aimed at regulating IDO1 activity and yields insight into heme-dependent dioxygenation chemistry.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013870
- Subject Headings
- Lyases, Enzymes
- 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
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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.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013857
- Subject Headings
- Marine natural products, Diterpenoids, Biomimetics, Soft corals
- Format
- Document (PDF)
- Title
- Discovery and investigation of survivin-targeting marine natural products from Ellisella paraplexauroides and Eudistoma olivaceum.
- Creator
- Francis, Kirstie Tandberg, Wright, Amy E., Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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In 2020, the National Institute of Health reported that more than 1.8 million people in the U.S. were diagnosed with cancer and over half a million died from those diseases. There is an urgent need for innovative and effective new treatments which stem from novel cancer drug targets. Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is highly expressed during development and in cancer cells but not in differentiated tissues, making it a tumor-selective target...
Show moreIn 2020, the National Institute of Health reported that more than 1.8 million people in the U.S. were diagnosed with cancer and over half a million died from those diseases. There is an urgent need for innovative and effective new treatments which stem from novel cancer drug targets. Survivin, the smallest member of the inhibitor of apoptosis protein (IAP) family, is highly expressed during development and in cancer cells but not in differentiated tissues, making it a tumor-selective target for new drug therapies. At only 16.5 kDa, it consists of a single Baculovirus IAP Repeat (BIR) domain and an α-helical coiled coil. Survivin plays a multitude of roles in the growth and survival of cancer cells—which can be attributed to the variable cellular localizations and posttranslational modifications of the protein—including inhibition of apoptosis, mitosis and cell cycle progression, DNA damage repair, drug resistance, metastasis, angiogenesis, and cell senescence, among others. A drug that is able to target surviving transcription or posttranslational modification or disrupt one of these critical pathways may serve as an attractive new cancer therapy. Despite decades of research on surviving and its intracellular functions, researchers have yet to find an FDA approved drug. Using a high throughput approach, Harbor Branch Oceanographic Institute’s chemical library of marine natural products was screened by the Guzmán lab to identify compounds capable of downregulating survivin expression in A549 non-small cell lung carcinoma and DLD-1 colorectal adenocarcinoma cell lines. From the screening assay, pure compounds were identified which reduce levels of survivin protein in cancer cells. Chapter 2 describes the isolation and structure elucidation of five polyhydroxylated sterol analogs from Ellisella paraplexauroides, four of them novel. Chapter 3 describes the isolation and structure elucidation of two compounds from Eudistoma olivaceum, eudistomin H and I. Chapter 4 describes the secondary biological testing employed to determine if the reduction of survivin expression was driven by reducing de novo production or increasing the degradation of existing protein by evaluating differential gene expression of survivin mRNA using reverse transcriptase quantitative polymerase chain reaction and measuring degradation rates of survivin protein, respectively.
Show less - Date Issued
- 2021
- PURL
- http://purl.flvc.org/fau/fd/FA00013828
- Subject Headings
- Survivin, Marine natural products, Antineoplastic agents--Development
- Format
- Document (PDF)
- Title
- A STUDY ON THE CLINICAL RELEVANCE OF METALLOPROTEINASE INHIBITION.
- Creator
- Onwuha-Ekpete, Lillian, Fields, Gregg, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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The Metzincins are a superfamily of zinc-dependent endopeptidases associated with the regulation of the extracellular matrix (ECM). Their members include A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs), A Disintegrin and Metalloproteinases (ADAMs), and the matrix metalloproteinases (MMPs). Metzincins exhibit diverse functions associated with both physiological and pathological states that include the proteolytic degradation of the ECM, regulation of various growth...
Show moreThe Metzincins are a superfamily of zinc-dependent endopeptidases associated with the regulation of the extracellular matrix (ECM). Their members include A Disintegrin and Metalloproteinase with Thrombospondin Motifs (ADAMTSs), A Disintegrin and Metalloproteinases (ADAMs), and the matrix metalloproteinases (MMPs). Metzincins exhibit diverse functions associated with both physiological and pathological states that include the proteolytic degradation of the ECM, regulation of various growth factors, cell surface receptors, and chemokines, and mediation of biological functions such as extravasation, survival, and proliferation. In pathological conditions such as cancer associated with chronic inflammation and multiple sclerosis associated with neurodegeneration, dysregulation of Metzincin activities are a hallmark of disease progression and severity. Hence, Metzincins are therapeutic targets for various disease states and research into optimal Metzincin inhibitor design is an ongoing exploit.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013615
- Subject Headings
- Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, T cells, Immunology
- 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
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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.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013565
- Subject Headings
- Prion Diseases, Prions--pathogenicity, Amyloid, Peptides, Prions
- Format
- Document (PDF)
- 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
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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.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013514
- Subject Headings
- Calcitonin, Amyloid
- 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
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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.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013539
- Subject Headings
- Marine natural products, Diterpenoids, Biomimetics
- Format
- Document (PDF)
- Title
- Synthesis of Fluorogenic Probes Specific for Matrix Metalloproteinase 13.
- Creator
- Ibrahim, Mariam, Fields, Gregg B., Leventouri, Theodora, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Matrix Metalloproteinase-13 (MMP-13) belongs to a large family of proteolytic enzymes which are characterized by their ability to degrade the extracellular matrix components. MMP-13 appears to have a critical role in tumor invasion and metastasis. In this study, several fluorogenic probes specific for MMP-13 were designed and characterized. These synthesized probes could be modified with chelators to be applied for imaging MMP-13 in breast cancer and/or multiple myeloma models. The activity...
Show moreMatrix Metalloproteinase-13 (MMP-13) belongs to a large family of proteolytic enzymes which are characterized by their ability to degrade the extracellular matrix components. MMP-13 appears to have a critical role in tumor invasion and metastasis. In this study, several fluorogenic probes specific for MMP-13 were designed and characterized. These synthesized probes could be modified with chelators to be applied for imaging MMP-13 in breast cancer and/or multiple myeloma models. The activity and selectivity of MMP-13 and other MMPs against these probes were studied through two approaches. It was found that these probes were cleaved by all MMPs, but MMP-13 showed the highest activity and selectivity towards these peptides.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013507
- Subject Headings
- Matrix Metalloproteinases, Peptides, Fluorogenic probes
- Format
- Document (PDF)
- Title
- PHOSPHORUS SEQUESTRATION AND BIOREMEDIATION: PHOSPHORUS-31 NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY.
- Creator
- Duersch, Bobby G., Louda, J. William, Florida Atlantic University, Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
- Abstract/Description
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Eutrophication is an increase in primary plant nutrients (Nitrogen [N] and Phosphorus [P]) in oceans, estuaries and lakes. The consequences of eutrophication are harmful algal blooms (HABs), resulting in algal toxin production and the depletion of oxygen as the extensive biomass decays. P is often the limiting nutrient and is viewed as a significant environmental problem. Most of the excess P that enters aquatic ecosystems originates from anthropogenic sources such as fertilizers, sewage,...
Show moreEutrophication is an increase in primary plant nutrients (Nitrogen [N] and Phosphorus [P]) in oceans, estuaries and lakes. The consequences of eutrophication are harmful algal blooms (HABs), resulting in algal toxin production and the depletion of oxygen as the extensive biomass decays. P is often the limiting nutrient and is viewed as a significant environmental problem. Most of the excess P that enters aquatic ecosystems originates from anthropogenic sources such as fertilizers, sewage, animal wastes, compost, crop residues, and wastewater. Over time, one of the main reservoirs of P becomes organic P (Po). We investigated the chemical nature and dynamics of P in cyanobacteria, horse manure, stormwater treatment areas, and rice fields. To better understand the chemical nature of P, the identification of specific P compounds was required, which was achieved through 31P nuclear magnetic resonance (NMR) spectroscopy. We investigated how paramagnetic metals and quadrupolar nuclei cause severe line broadening, peak shifts, and decreased the signal to noise ratio. Results revealed that certain Po forms are readily bioavailable to Microcystis aeruginosa. Additionally, the potential heterotrophic use of the organic portion (e.g., glucose, glycerol) of these P compounds are indicated for the growth and persistence of Microcystis aeruginosa. We showed that the cultivation of rice (Oryza sativa L.) had been found to effectively reduce P from agrarian soil and water through plant uptake and, therefore, minimizing downstream eutrophication. Soil, water, sugarcane, and rice plants at two different stages were analyzed for twelve different elements. Finally, we examined how a “relic” agrarian ditch in Stormwater Treatment Area 1 East (STA-1E) can be used for the retention and sequestration of P and other nutrients. The STAs were established to capture P from agricultural and other sources before reaching the Everglades. Retained P is primarily stored in the wetland soils and sediments, generated through a collection of interrelated physical, chemical, and biological processes.
Show less - Date Issued
- 2020
- PURL
- http://purl.flvc.org/fau/fd/FA00013594
- Subject Headings
- Nuclear magnetic resonance spectroscopy, Eutrophication, Phosphorus--Environmental aspects, Bioremediation
- Format
- Document (PDF)