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Title: Polydiscamide A: a new bioactive depsipeptide from the marine sponge Discodermia sp.
Creator: Gulavita, N. K., Gunasekera, Sarath P., Pomponi, Shirley A., Robinson, E. V.
Date Issued: 1992
PURL: http://purl.flvc.org/FCLA/DT/3332992
Subject Headings: Sponges, Depsipeptides, Peptides, Cyclic
Format: Document (PDF)

Title: Cytotoxic peptides from marine sponges.
Creator: Gulavita, N. K., Wright, Amy E., McCarthy, Peter J., Pomponi, Shirley A., Longley, Ross E.
Date Issued: 1996
PURL: http://purl.flvc.org/fau/fd/FA00007341
Subject Headings: Sponges, Peptides, Cytotoxins, Stereochemistry
Format: Document (PDF)

Title: Characterization of Disulfide Constrained Natural Peptides.
Creator: Hoggard, Mickelene F., Cudic, Mare, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: The use of peptide drugs has gained popularity recently. Peptides are attractive drug targets due to their high specificity and potency towards their biological targets. A drawback for peptide drugs is a lack of stability for oral delivery. Two classes of disulfide-rich peptides, conotoxins and cyclotides, have been shown to have higher stability than linear peptides thanks to their disulfide connectivity. Conotoxins are present in the venom of cone snails, a carnivorous marine mollusk that...
Show moreThe use of peptide drugs has gained popularity recently. Peptides are attractive drug targets due to their high specificity and potency towards their biological targets. A drawback for peptide drugs is a lack of stability for oral delivery. Two classes of disulfide-rich peptides, conotoxins and cyclotides, have been shown to have higher stability than linear peptides thanks to their disulfide connectivity. Conotoxins are present in the venom of cone snails, a carnivorous marine mollusk that preys upon fish, worms, or other mollusks. Conotoxins are promising drugs leads with great prospects in the treatment of diseases and disorders such as chronic pain, multiple sclerosis and Parkinson’s and Alzheimer’s diseases. Cyclotides, which are cyclic cysteine knot containing peptides, isolated from the Violaceae (violet), Rubiaceae (coffee), and Cucurbitaceae (cucurbit) families and they have a wide range of biological activities, such as anti-HIV, uterotonic, and antimicrobial. P-superfamily framework IX conotoxins (C-C- C-CXC- C) contain the same cysteine framework, homologous sequences, and similar 3D structures to cyclotides. The knot containing conotoxins have been identified in several Conus species, but this work focuses on those from Conus brunneus, Conus purpurascens, and Conus gloriamaris. The cysteine knot motif of cyclotides and P-superfamily conotoxins is characterized by a cyclic backbone and six-conserved cysteine residues that form the three-disulfide bridges of the “knot”. This motif provides cyclotides and conotoxins with superior stability against thermal, chemical, and enzymatic degradation; marking them as potential frameworks for peptide drug delivery. Presented are details on the isolation of conotoxins and cyclotides, from Viola tricolor, and the characterization of their activity in the well-characterized Drosophila melanogaster giant fiber system (GFS) neuronal circuit, which contains GAP, acetylcholine, and glutamate synapses. The transcriptomes of two Conus brunneus specimens were assembled and mined for P-superfamily framework IX conotoxins. Eleven mature P-superfamily framework IX conotoxins were identified in the crude venom.
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Date Issued: 2018
PURL: http://purl.flvc.org/fau/fd/FA00005955
Subject Headings: Peptide drugs, Cyclotides, Conotoxins
Format: Document (PDF)

Title: Isolation and structure elucidation of Perthamide B, a novel peptide from the sponge Theonella sp.
Creator: Gulavita, N. K., Pomponi, Shirley A., Wright, Amy E., Yarwood, Donna, Sills, Matthew A.
Date Issued: 1994
PURL: http://purl.flvc.org/FCLA/DT/3331880
Subject Headings: Sponges, Cyclic peptides, Peptides--Structure, Spectroscopic techniques
Format: Document (PDF)

Title: Cyclic lipodepsipeptides as lead structures for the discovery of new antiobiotics.
Creator: Bionda, Nina., Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: With antimicrobial resistance to current drugs steadily rising, the development of new antibiotics with novel mechanisms of action has become an imperative. The majority of life-threatening infections worldwide are caused by "ESKAPE" pathogens which are encountered in more than 40% of hospital-acquired infections, and are resistant to the majority of commonly used antibiotics. Naturally occurring cyclic depsipeptides, microbial secondary metabolites that contain one or more ester bonds in...
Show moreWith antimicrobial resistance to current drugs steadily rising, the development of new antibiotics with novel mechanisms of action has become an imperative. The majority of life-threatening infections worldwide are caused by "ESKAPE" pathogens which are encountered in more than 40% of hospital-acquired infections, and are resistant to the majority of commonly used antibiotics. Naturally occurring cyclic depsipeptides, microbial secondary metabolites that contain one or more ester bonds in addition to amide bonds, have emerged as an important source of pharmacologically active compounds or lead structures for the development of novel antibiotics. Some of those peptides are either already marketed (daptomycin) or in advanced stages of clinical development (ramoplanin). Structurally simple, yet potent, fusaricidin/LI-F and lysobactin families of naturally occurring antibiotics represent particularly attractive candidates for the development of new antibacterial agents capable of overco ming infections caused by multidrug-resistant bacteria. These natural products exhibit potent antimicrobial activity against a variety of clinically relevant fungi and Gram-positive bacteria. Therefore, access to these classes of natural products and their synthetic analogs, combined with elucidation of their mode of action represent important initial steps toward full exploitation of their antmicrobial potential. This dissertation describes a general approach toward the solid-phase synthesis of fusaricidin/LI-F and lysobactin analogs and an extensive structure-activity relationship (SAR) study. We have devised a simple and robust preparation strategy based on standard Fmoc solid-phase peptide synthesis protocols., The SAR study revealed key structural requirements for fusaricidin/LI-F and related cyclic lipopeptides antibacterial activity, including the presence of the guanidino moietly at the end of the lipidic tail, hydrophobic amino acid residues, and peptide conformation Moreover, substitution of the ester bond with an amide bond significantly improved stability under physiologically relevant conditions and reduced toxicity. In addition, we have shown that these antibacterial peptides exert their mode of action via a novel mechanism, which invloves bacterial membrane interactions, followed by peptide internalization. Altogether, the research described in this dissertation demonstrates that new antibiotics derived from fusaricidin/LI-F natural products, have the potential to meet the challenge of antibiotic resistance in Gram-positive bacteria.
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Date Issued: 2013
PURL: http://purl.flvc.org/FAU/3360768
Subject Headings: Microbial peptides, Drugs, Design, Peptides, Therapeutic use, Genetic engineering, Antibacterial agents, Peptide antibiotics, Research, Methodology, Peptide antibiotics, Analysis
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: 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.
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Date Issued: 2020
PURL: http://purl.flvc.org/fau/fd/FA00013507
Subject Headings: Matrix Metalloproteinases, Peptides, Fluorogenic probes
Format: Document (PDF)

Title: Comparison of alkyl-bonded alumina-based stationary phases for peptide separation by high performance liquid chromatography.
Creator: Ramdial, Nirmala Debra-Ann, Florida Atlantic University, Haky, Jerome E., Department of Chemistry and Biochemistry, Charles E. Schmidt College of Science
Abstract/Description: The performance of several alkyl-bonded alumina-based stationary phases was evaluated by comparing the separation of synthetic octapeptide and polypeptide mixtures and tryptic digests of larger proteins. These phases were of differing pore diameter, alkyl chain length modification and particle shape and size. The separations were compared to standard silica phases. The narrow pore octadecyl bonded alumina phase outperformed the other alumina and silica phases in terms of separation efficiency...
Show moreThe performance of several alkyl-bonded alumina-based stationary phases was evaluated by comparing the separation of synthetic octapeptide and polypeptide mixtures and tryptic digests of larger proteins. These phases were of differing pore diameter, alkyl chain length modification and particle shape and size. The separations were compared to standard silica phases. The narrow pore octadecyl bonded alumina phase outperformed the other alumina and silica phases in terms of separation efficiency and mobile phase resistance. Superior performance is attributed to the enhanced solute mass transfer properties and the unique morphology of the microplatelet alumina particles. The mechanism of separation gradually changes with increasing size of the peptide.
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Date Issued: 1992
PURL: http://purl.flvc.org/fcla/dt/14831
Subject Headings: Peptides--Separation, Liquid chromatography
Format: Document (PDF)

Title: Study of Cell Penetrating Peptide Uptake and Cancer Cell Discrimination with Raman Spectroscopy and Microscopy.
Creator: Cosme, Patrick Jason, Terentis, Andrew C., Florida Atlantic University, Charles E Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cell penetrating peptides (CPPs) are short sequences of amino acids that excel in crossing the cellular membrane without inducing cytotoxicity Interest in these peptides stem from their ability to be attached, and grant their penetrating properties to, a variety of cargo In this work we have combined the application of Confocal Raman Microscopy (CRM) and Atomic Force Microscopy for the first time to examine the interactions of unlabeled Transportan (TP), one of the most well studied CPPs,...
Show moreCell penetrating peptides (CPPs) are short sequences of amino acids that excel in crossing the cellular membrane without inducing cytotoxicity Interest in these peptides stem from their ability to be attached, and grant their penetrating properties to, a variety of cargo In this work we have combined the application of Confocal Raman Microscopy (CRM) and Atomic Force Microscopy for the first time to examine the interactions of unlabeled Transportan (TP), one of the most well studied CPPs, with mammalian cells CRM’s capability to discriminate control and treated cell groups was verified by principal component analysis (PCA) and linear discriminant analysis (LDA) and was 93-100% accurate We’ve determined that at a concentration of 20 μM TP enters cells through a non-endocytotic mechanism, has a high affinity for the cytoplasm and membranes, and results in a significant increase in cellular stiffness Our work provides the first direct evidence of this cell-stiffening phenomenon SFTI-1, the smallest member of a bicyclic, cysteine rich class of CPPs, was examined by CRM to determine the potential role of cyclic structure on cellular uptake The peptide, along with monocyclic and linear analogs was heavy isotope labeled and incubated with mammalian cells at numerous concentrations and timespans Our work is the first SFTI-1 uptake study forgoing the use of fluorophore conjugates, which have been linked to artificial cellular uptake We demonstrate herein the absence of any CRM detectable uptake, providing the first evidence that SFTI-1 may not be a CPP Finally, CRM was applied to the discrimination of normal and basal cell carcinoma cells obtained from the same donor The use of patient matched cells avoids the normal biochemical variations that exist among individuals, ensuring that discrimination is based solely on the cell’s diseased state CRM spectra, analyzed by PCA and LDA, were capable of spectral discrimination with 100% accuracy Major differences in the cancerous cells were an increase in lipids and nucleic acids, and an overall decrease in protein We also demonstrate an enhancement in Raman signal through the use of an aluminum foil substrate, providing a practical approach for measuring cells with thin morphologies
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Date Issued: 2016
PURL: http://purl.flvc.org/fau/fd/FA00004756
Subject Headings: Peptides--Analysis, Peptides--Therapeutic use, Peptides--Physiological transport, Cellular signal transduction, Raman spectroscopy, Infrared spectroscopy
Format: Document (PDF)

Title: Discobahamins A and B, new peptides from the Bahamian deep water marine sponge Discodermia sp.
Creator: Gunasekera, Sarath P., Pomponi, Shirley A., McCarthy, Peter J.
Date Issued: 1994
PURL: http://purl.flvc.org/FCLA/DT/3333010
Subject Headings: Sponges, Peptides, Marine natural products, Chemical structure
Format: Document (PDF)

Title: Kapakahine B, a cyclic hexapeptide with an alpha-carboline ring system from the marine sponge Cribrochalina olemda.
Creator: Nakao, Y., Yeung, Bryan K. S., Yoshida, W. Y., Scheuer, P. J., Kelly-Borges, M., Harbor Branch Oceanographic Institute
Date Issued: 1995
PURL: http://purl.flvc.org/FCLA/DT/3319086
Subject Headings: Indole alkaloids, Sponges --Research, Carbolines, Cyclic peptides
Format: Document (PDF)

Title: The Kapakahines, cyclic peptides from the marine sponge Cribrochalina olemda.
Creator: Yeung, Bryan K. S., Nakao, Y., Kinnel, R. B., Carney, J. R., Yoshida, W. Y., Scheuer, P. J., Harbor Branch Oceanographic Institute
Date Issued: 1996
PURL: http://purl.flvc.org/FCLA/DT/3319098
Subject Headings: Sponges --Research, Marine natural products, Cyclic peptides
Format: Document (PDF)

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

Title: Discovery and biological characterization of conotoxins from the venom of Conus Brunneus in Drosophila Melanogaster.
Creator: Heghinian, Mari D., Mari, Frank, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Cone snails are venomous marine predators whose venom is a complex mixture of modified peptides (conopeptides). Conopeptides have direct specificity towards voltage- and ligand-gated ion channels and G-protein coupled receptors. More specifically, alpha conotoxins target nicotinic acetylcholine receptors (nAChR) and are of great interest as probes for different nAChR subtypes involved in a broad range of neurological function. Typically, the amount of peptide provided directly from the cone...
Show moreCone snails are venomous marine predators whose venom is a complex mixture of modified peptides (conopeptides). Conopeptides have direct specificity towards voltage- and ligand-gated ion channels and G-protein coupled receptors. More specifically, alpha conotoxins target nicotinic acetylcholine receptors (nAChR) and are of great interest as probes for different nAChR subtypes involved in a broad range of neurological function. Typically, the amount of peptide provided directly from the cone snails (from either dissected or “milked” venom) is minimal, thus hindering the wide use of bioassay-guided approaches for compound discovery. Biochemical-based approaches for discovery by means of identification and characterization of venom components can be used due to their compatibility with the small quantities of cone snail venom available; however, no direct assessment of the bioactivity can be gleaned from these approaches. Therefore, newly discovered conotoxins must be acquired synthetically, which can be difficult due to their complicated folding motifs. The ability to test small quantities of peptide for bioactivity during the purification process can lead to the discovery of novel components using more direct approaches. Presented here is the description of use of an effective method of bioassay-guided fractionation for the discovery of novel alpha conotoxins as well as further biological characterization of other known alpha conotoxins. This method requires minimal amounts of sample and evaluates, via in vivo electrophysiological measurements, the effect of conotoxins on the functional outputs of a well-characterized neuronal circuit in Drosophila melanogaster known as the giant fiber system. Our approach uses reversed-phase HPLC fractions from venom dissected from the ducts of Conus brunneus in addition to synthetic alpha conotoxins. Fractions were individually tested for activity, re-fractionated, and re-tested to narrow down the compound responsible for activity. A novel alpha conotoxin, bru1b, was discovered via the aforementioned approach. It has been fully characterized in the giant fiber system through the use of mutant flies, as well as tested in Xenopus oocytes expressing nicotinic acetylcholine channels and against the acetylcholine binding protein. Other well-known alpha conotoxins have also been characterized in the giant fiber system.
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Date Issued: 2014
PURL: http://purl.flvc.org/fau/fd/FA00004122, http://purl.flvc.org/fau/fd/FA00004122
Subject Headings: Drosophila melanogaster, Gastropoda -- venom, Peptides -- Structure, Venom
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: 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: Role of the N-Terminal Hydrophilic Region of Amyloid Beta Peptide in Amyloidogenesis, Membrane Interaction and Toxicity Associated with Alzheimer’s Disease.
Creator: Morris, Clifford M., Du, Deguo, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Chemistry and Biochemistry
Abstract/Description: Alzheimer’s disease (AD) is a deleterious neurodegenerative disease caused in major part by the aberrant processing and accumulation of amyloid beta peptides. In this dissertation, we systematically investigated the role of N-terminal region (NTR) residues of amyloid (1-40) (Aβ40) peptide in amyloidogenesis, lipid bilayer membrane interaction and damage, as well as neurotoxicity. Herein, we investigated the role of NTR residues on the aggregation and amyloid fibril formation process, to gain...
Show moreAlzheimer’s disease (AD) is a deleterious neurodegenerative disease caused in major part by the aberrant processing and accumulation of amyloid beta peptides. In this dissertation, we systematically investigated the role of N-terminal region (NTR) residues of amyloid (1-40) (Aβ40) peptide in amyloidogenesis, lipid bilayer membrane interaction and damage, as well as neurotoxicity. Herein, we investigated the role of NTR residues on the aggregation and amyloid fibril formation process, to gain understanding on the electrostatic and hydrophobic constituents of the mechanism. This was achieved by substituting specific charged residues located in the NTR of Aβ40 and investigating their effects through a variety of techniques. We also investigated the role of NTR charged residues in their interaction with supported phospholipid bilayer membranes through the use of Quartz Crystal Microbalance with Dissipation (QCM-D) monitoring to gain insight on the mechanistic details of the interaction. To further understand the implications of substituting charged NTR residues on membrane interaction, pore formation and damage, we utilized a carboxyfluorescein dye leakage assay to quantify the membrane damage caused by Aβ40 and the NTR mutants. We also performed neurotoxicity assay with SH-SY5Y neuroblastoma cells to shed light on the effects of NTR substitutions on cellular toxicity. Finally, we synthesized a polymer, trimethyl chitosan (TMC), and utilized it as a polyelectrolyte monitor of electrostatic interactions occurring between TMC and the NTR of Aβ40. Our results demonstrate that the NTR charged residues of Aβ40 contribute significantly to the aggregation process, amyloidogenesis, and phospholipid membrane interaction and perturbation by means of electrostatic, thermodynamic and hydrophobic forces.
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Date Issued: 2019
PURL: http://purl.flvc.org/fau/fd/FA00013246
Subject Headings: Alzheimer's disease, Amyloid beta-Peptides, Amyloid
Format: Document (PDF)

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

Title: Biophysical characterization of bioactive peptide amphiphiles.
Creator: Fishel, Ayala, Florida Atlantic University, Fields, Gregg B.
Abstract/Description: In this present work we have examined the biophysical characterization of two peptides. One alpha-helical (SPARC) and the other triple-helical (collagen). We have compared the effect of lipidation on stabilizing of the alpha-helical and triple-helical peptides. For the first peptide, amino acids from the angiogenesis-inducing region of SPARC were incorporated into alpha-helical peptide sequence. A Tyr was placed between the alpha-helical sequence and the peptide to provide a chromophore; Lys...
Show moreIn this present work we have examined the biophysical characterization of two peptides. One alpha-helical (SPARC) and the other triple-helical (collagen). We have compared the effect of lipidation on stabilizing of the alpha-helical and triple-helical peptides. For the first peptide, amino acids from the angiogenesis-inducing region of SPARC were incorporated into alpha-helical peptide sequence. A Tyr was placed between the alpha-helical sequence and the peptide to provide a chromophore; Lys-Ala-Glu-Ile-Glu-Ala-Leu-Lys-Ala-Glu-Ile-Glu-Ala-Leu-Lys-Ala-Tyr-Lys-His-Gly-Lys-NH 2 was the final sequence. For the second peptide, the sequence chosen to mimic the alpha2beta1 integrin binding site in type I collagen was (Gly-Pro-Hyp)4-Gly-Pro-Ala-Gly-Lys-Asp-Gly-Glu-Ala-Gly-Ala-Gln-(Gly-Pro-Hyp) 4-NH2. Next, each peptide was lipidated with a C-16 acid and was biophysically characterized to determine physiological compatibility. Techniques used included circular dichroism spectroscopy, gel electrophoresis, and Fourier transform infrared spectroscopy. Lastly, one of the peptide amphiphiles was examined as a biomaterial modifier.
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Date Issued: 2000
PURL: http://purl.flvc.org/fcla/dt/15780
Subject Headings: Peptides--Synthesis, Lipids, Bioactive compounds
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: 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).
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014154
Subject Headings: Antibodies, Peptides, Biochemistry, β-Hairpins
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: 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.
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Date Issued: 2023
PURL: http://purl.flvc.org/fau/fd/FA00014294
Subject Headings: Amyloid beta-Peptides, Alzheimer's disease
Format: Document (PDF)

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