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Full-Text Articles in Social and Behavioral Sciences
Extracellular Adenosine 5'-Triphosphate And Lipopolysaccharide Induce Interleukin-1Β Release In Canine Blood, Mari Spildrejorde, Stephen J. Curtis, Belinda L. Curtis, Ronald Sluyter
Extracellular Adenosine 5'-Triphosphate And Lipopolysaccharide Induce Interleukin-1Β Release In Canine Blood, Mari Spildrejorde, Stephen J. Curtis, Belinda L. Curtis, Ronald Sluyter
Faculty of Science, Medicine and Health - Papers: part A
Binding of extracellular adenosine 5′-triphosphate (ATP) or lipopolysaccharide (LPS) to the damage-associated molecular pattern receptor P2X7 or the pathogen-associated molecular pattern receptor Toll-like receptor (TLR)4, respectively, can induce the release of the pleiotropic cytokine interleukin (IL)-1β in humans and mice. However, the release of IL-1β in dogs remains poorly defined. Using a canine IL-1β enzyme-linked immunosorbent assay, this study investigated whether ATP or LPS could induce IL-1β release in a canine blood-based assay. Short-term incubations (30 min) with ATP induced IL-1β release in LPS-primed canine blood, and this process could be near-completely impaired by the P2X7 antagonist, A438079. In contrast, …
Diarylacylhydrazones: Clostridium-Selective Antibacterials With Activity Against Stationary-Phase Cells, Chao Chen, Naveen K. Dolla, Gabriele Casadei, John B. Bremner, Kim Lewis, Michael J. Kelso
Diarylacylhydrazones: Clostridium-Selective Antibacterials With Activity Against Stationary-Phase Cells, Chao Chen, Naveen K. Dolla, Gabriele Casadei, John B. Bremner, Kim Lewis, Michael J. Kelso
Faculty of Science, Medicine and Health - Papers: part A
Current antibiotics for treating Clostridium difficile infections (CDI), that is, metronidazole, vancomycin and more recently fidaxomicin, are mostly effective but treatment failure and disease relapse remain as significant clinical problems. The shortcomings of these agents are attributed to their low selectivity for C. difficile over normal gut microflora and their ineffectiveness against C. difficile spores. This Letter reports that certain diarylacylhydrazones identified during a high-throughput screening/counter-screening campaign show selective activity against two Clostridium species (C. difficile and Clostridium perfringens) over common gut commensals. Representative examples are shown to possess activity similar to vancomycin against clinical C. difficile strains and to …
Synthesis And In Vitro Evaluation Of Tetrahydroisoquinolines With Pendent Aromatics As Sigma-2 (Σ2) Selective Ligands, Mark E. Ashford, Vu H. Nguyen, Ivan Greguric, Tien Q. Pham, Paul A. Keller, Andrew Katsifis
Synthesis And In Vitro Evaluation Of Tetrahydroisoquinolines With Pendent Aromatics As Sigma-2 (Σ2) Selective Ligands, Mark E. Ashford, Vu H. Nguyen, Ivan Greguric, Tien Q. Pham, Paul A. Keller, Andrew Katsifis
Faculty of Science, Medicine and Health - Papers: part A
5-Bromo-N-[4-(6,7-dimethoxy-3,4-dihydro-1H-isoquinolin-2-yl)-butyl)]-2,3-dimethoxybenzamide 1 is a potent and selective σ2 receptor ligand suitable for further development. A series of new analogues, incorporating a variety of isoquinoline and carboxylic acid moieties, linked together with either a linear or cyclic amine spacer have been synthesised and assessed for their σ1/σ2 binding affinity and selectivity. Compounds with a rigid piperidine spacer gave Ki values for the σ2 receptor between 8.7–845 nM. Changing the configuration of the methoxy groups on the isoquinoline moiety resulted in molecules with σ2Ki values of 4.4–133 nM whereas varying the length and flexibility of the carbon spaces gave σ2Ki values 0.88–15.0 …
The Use Of Immobilised Metal Affinity Chromatography (Imac) To Compare Expression Of Copper-Binding Proteins In Control And Copper-Exposed Marine Microalgae, Cassandra L. Smith, Jenny L. Stauber, Mark R. Wilson, Dianne F. Jolley
The Use Of Immobilised Metal Affinity Chromatography (Imac) To Compare Expression Of Copper-Binding Proteins In Control And Copper-Exposed Marine Microalgae, Cassandra L. Smith, Jenny L. Stauber, Mark R. Wilson, Dianne F. Jolley
Faculty of Science, Medicine and Health - Papers: part A
Toxicity of metals to aquatic organisms is dependent on both external factors, such as exposure concentration and water quality parameters, and intracellular processes including specific metal-binding sites and detoxification. Current models used to predict copper toxicity in microalgae do not adequately consider these intracellular processes. This study compared the copper-binding proteins from four species of marine microalgae, Dunaliella tertiolecta, Tetraselmis sp., Phaedactylum tricornutum and Ceratoneis closterium, in controls (no added copper) and following a 72-h exposure to copper (sufficient to inhibit growth by approximately 50 %). Cells were lysed by sonication, which was optimised to obtain 54–94 % cell rupture …
Factors Governing The Rejection Of Trace Organic Contaminants By Nanofiltration And Reverse Osmosis Membranes, Hai Q. Dang, Long D. Nghiem, William E. Price
Factors Governing The Rejection Of Trace Organic Contaminants By Nanofiltration And Reverse Osmosis Membranes, Hai Q. Dang, Long D. Nghiem, William E. Price
Faculty of Science, Medicine and Health - Papers: part A
This study aimed to elucidate key factors governing the rejection of trace organic contaminants (TrOCs) by nanofiltration (NF) and reverse osmosis (RO) membranes. The rejection of 16 selected hydrophilic and hydrophobic TrOCs by an NF and an RO membranes was evaluated at different solution pH values using a cross-flow NF/RO filtration system. An analytical technique consisting of solid phase extraction followed by gas chromatography and mass spectrometry detection was used for the analysis of the TrOCs. In general, rejection increased in the order of decreasing membrane permeability, increasing molecular weight (or equivalent molecular width) of the TrOCs, and increasing hydrophilicity. …
Pka Cycling Of The General Acid/Base In Glycoside Hydrolase Families 33 And 34, Haibo Yu, Thomas M. Griffiths
Pka Cycling Of The General Acid/Base In Glycoside Hydrolase Families 33 And 34, Haibo Yu, Thomas M. Griffiths
Faculty of Science, Medicine and Health - Papers: part A
Glycoside hydrolase families 33 and 34 catalyse the hydrolysis of terminal sialic acid residues from sialyl oligosaccharides and glycoconjugates with a net retention of the stereochemistry at the anomeric centre. It is generally believed that the conserved aspartic acid in the active site functions as a general acid to protonate the hydroxyl group of the departing aglycone during glycosylation, and then as a general base to facilitate the nucleophilic attack of the water molecule on the intermediate state during the deglycosylation reaction. The dual role of the general acid/base places specific demands upon its protonation state, and thus pKa values. …
Discovery Of Lead Compounds Targeting The Bacterial Sliding Clamp Using A Fragment-Based Approach, Zhou Yin, Louise Whittell, Yao Wang, Slobodan Jergic, Michael Liu, Elizabeth J. Harry, Nicholas Dixon, Jennifer Beck, Michael Kelso, Aaron Oakley
Discovery Of Lead Compounds Targeting The Bacterial Sliding Clamp Using A Fragment-Based Approach, Zhou Yin, Louise Whittell, Yao Wang, Slobodan Jergic, Michael Liu, Elizabeth J. Harry, Nicholas Dixon, Jennifer Beck, Michael Kelso, Aaron Oakley
Faculty of Science, Medicine and Health - Papers: part A
The bacterial sliding clamp (SC), also known as the DNA polymerase III β subunit, is an emerging antibacterial target that plays a central role in DNA replication, serving as a protein–protein interaction hub with a common binding pocket to recognize linear motifs in the partner proteins. Here, fragment-based screening using X-ray crystallography produced four hits bound in the linear-motif-binding pocket of the Escherichia coli SC. Compounds structurally related to the hits were identified that inhibited the E. coli SC and SC-mediated DNA replication in vitro. A tetrahydrocarbazole derivative emerged as a promising lead whose methyl and ethyl ester prodrug forms …
Chikungunya Virus: Emerging Targets And New Opportunities For Medicinal Chemistry, Adel Rashad, Suresh Mahalingam, Paul Keller
Chikungunya Virus: Emerging Targets And New Opportunities For Medicinal Chemistry, Adel Rashad, Suresh Mahalingam, Paul Keller
Faculty of Science, Medicine and Health - Papers: part A
Chikungunya virus is an emerging arbovirus that is widespread in tropical regions and is spreading quickly to temperate climates with recent epidemics in Africa and Asia and documented outbreaks in Europe and the Americas. It is having an increasingly major impact on humankind, with potentially life-threatening and debilitating arthritis. There is no treatment available, and only in the past 24 months have lead compounds for development as potential therapeutics been reported. This Perspective discusses the chikungunya virus as a significant, new emerging topic for medicinal chemistry, highlighting the key viral target proteins and their molecular functions that can be used …
Total Synthesis Of Hyacinthacines B3, B4, And B 5 And Purported Hyacinthacine B7, 7-Epi-Hyacinthacine B7, And 7a-Epi-Hyacinthacine B3 From A Common Precursor, Kongdech Savaspun, Christopher W. G Au, Stephen G. Pyne
Total Synthesis Of Hyacinthacines B3, B4, And B 5 And Purported Hyacinthacine B7, 7-Epi-Hyacinthacine B7, And 7a-Epi-Hyacinthacine B3 From A Common Precursor, Kongdech Savaspun, Christopher W. G Au, Stephen G. Pyne
Faculty of Science, Medicine and Health - Papers: part A
The total synthesis of hyacinthacines B3, B4, and B5 and purported hyacinthacine B7, 7-epi-hyacinthacine B7, and 7a-epi-hyacinthacine B3 from a common anti-1,2-amino alcohol precursor is described. These syntheses confirmed that the proposed structures and absolute configurations of hyacinthacines B3, B4, and B5 were correct and disclosed that the proposed structure of hyacinthacine B7 was incorrect. Our synthetic and spectroscopic studies suggest that the natural hyacinthacines B5 and B7 are the same compounds; however, without access to authentic samples this cannot be unequivocally proven.
Hypochlorite-Induced Structural Modifications Enhance The Chaperone Activity Of Human Α2-Macroglobulin, Amy Wyatt, Janet Kumita, Richard W. Mifsud, Cherrie A. Gooden, Mark Wilson, Christopher M. Dobson
Hypochlorite-Induced Structural Modifications Enhance The Chaperone Activity Of Human Α2-Macroglobulin, Amy Wyatt, Janet Kumita, Richard W. Mifsud, Cherrie A. Gooden, Mark Wilson, Christopher M. Dobson
Faculty of Science, Medicine and Health - Papers: part A
Hypochlorite, an oxidant generated in vivo by the innate immune system, kills invading pathogens largely by inducing the misfolding of microbial proteins. Concomitantly, the nonspecific activity of hypochlorite also damages host proteins, and the accumulation of damaged (misfolded) proteins is implicated in the pathology of a variety of debilitating human disorders (e.g., Alzheimer's disease, atherosclerosis, and arthritis). It is well-known that cells respond to oxidative stress by up-regulating proteostasis machinery, but the direct activation of mammalian chaperones by hypochlorite has not, to our knowledge, been previously reported. In this study, we show that hypochlorite-induced modifications of human α2-macroglobulin (α2M) markedly …
Discovery Of In Silico Hits Targeting The Nsp3 Macro Domain Of Chikungunya Virus, Phuong Nguyen, Haibo Yu, Paul Keller
Discovery Of In Silico Hits Targeting The Nsp3 Macro Domain Of Chikungunya Virus, Phuong Nguyen, Haibo Yu, Paul Keller
Faculty of Science, Medicine and Health - Papers: part A
The recent emergence and re-emergence of alphaviruses, in particular the chikungunya virus (CHIKV), in numerous countries has invoked a worldwide threat to human health, while simultaneously generating an economic burden on affected countries. There are currently no vaccines or effective drugs available for the treatment of the CHIKV, and with few lead compounds reported, the vital medicinal chemistry is significantly more challenging. This study reports on the discovery of potential inhibitors for the nsP3 macro domain of CHIKV using molecular docking, virtual screening, and molecular dynamics simulations, as well as work done to evaluate and confirm the active site of …
Diffusive Gradients In Thin Films Technique Provide Robust Prediction Of Metal Bioavailability And Toxicity In Estuarine Sediments, Elvio D. Amato, Stuart Simpson, Chad Jarolimek, Dianne Jolley
Diffusive Gradients In Thin Films Technique Provide Robust Prediction Of Metal Bioavailability And Toxicity In Estuarine Sediments, Elvio D. Amato, Stuart Simpson, Chad Jarolimek, Dianne Jolley
Faculty of Science, Medicine and Health - Papers: part A
Many sediment quality assessment frameworks incorporate contaminant bioavailability as a critical factor regulating toxicity in aquatic ecosystems. However, current approaches do not always adequately predict metal bioavailability to organisms living in the oxidised sediment surface layers. The deployment of the diffusive gradients in thin films (DGT) probes in sediments allows labile metals present in pore waters and weakly-bound to the particulate phase to be assessed in a time-integrated manner in situ. In this study, relationships between DGT-labile metal fluxes within 5 mm of the sediment-water interface and lethal and sub-lethal effects to the amphipod Melita plumulosa were assessed in a …
P2x7 Receptor Activation Induces Cd62l Shedding From Human Cd4+ And Cd8+ T Cells, Ronald Sluyter, James S. Wiley
P2x7 Receptor Activation Induces Cd62l Shedding From Human Cd4+ And Cd8+ T Cells, Ronald Sluyter, James S. Wiley
Faculty of Science, Medicine and Health - Papers: part A
The P2X7 receptor is expressed on T cells, however knowledge of its presence and function on human CD4+ and CD8+ subsets is limited. Immunolabeling with an anti-human P2X7 monoclonal antibody and flow cytometry demonstrated that P2X7 is present on the cell-surface of peripheral blood CD4+ and CD8+ T cells. Time-resolved flow cytometry demonstrated that extracellular ATP induced ethidium+ uptake into both T cell subsets. Flow cytometric measurements also demonstrated that ATP induced the rapid loss of CD62L (L-selectin) from CD4+ and CD8+ T cells. ATP-induced ethidium+ uptake and CD62L shedding were dramatically impaired in CD4+ and CD8+ T cells homozygous …
Carbazole Alkaloids And Coumarins From The Roots Of Clausena Guillauminii, Chiramet Auranwiwat, Surat Laphookhieo, Kongkiat Trisuwan, Stephen G. Pyne, Thunwadee Ritthiwigrom
Carbazole Alkaloids And Coumarins From The Roots Of Clausena Guillauminii, Chiramet Auranwiwat, Surat Laphookhieo, Kongkiat Trisuwan, Stephen G. Pyne, Thunwadee Ritthiwigrom
Faculty of Science, Medicine and Health - Papers: part A
Two novel carbazole alkaloids, guillauminines A and B (1 and 2), and sixteen known compounds were isolated and identified from the acetone extract of Clausena guillauminii roots. Their structures were elucidated by spectroscopic methods. The cytotoxic, antimalarial and antimycobacterial activities of the isolated compounds were evaluated.
The P2x7 Receptor Channel: Recent Developments And The Use Of P2x7 Antagonists In Models Of Disease, Rachael Bartlett, Leanne Stokes, Ronald Sluyter
The P2x7 Receptor Channel: Recent Developments And The Use Of P2x7 Antagonists In Models Of Disease, Rachael Bartlett, Leanne Stokes, Ronald Sluyter
Faculty of Science, Medicine and Health - Papers: part A
The P2X7 receptor is a trimeric ATP-gated cation channel found predominantly, but not exclusively, on immune cells. P2X7 activation results in a number of downstream events, including the release of proinflammatory mediators and cell death and proliferation. As such, P2X7 plays important roles in various inflammatory, immune, neurologic and musculoskeletal disorders. This review focuses on the use of P2X7 antagonists in rodent models of neurologic disease and injury, inflammation, and musculoskeletal and other disorders. The cloning and characterization of human, rat, mouse, guinea pig, dog, and Rhesus macaque P2X7, as well as recent observations regarding the gating and permeability of …
Simultaneous Nitrification/Denitrification And Trace Organic Contaminant (Troc) Removal By An Anoxic-Aerobic Membrane Bioreactor (Mbr), Hop Phan, Faisal Ibney Hai, Jinguo Kang, Hoa Dam, Ren Zhang, William Price, Andreas Broeckmann, Long Nghiem
Simultaneous Nitrification/Denitrification And Trace Organic Contaminant (Troc) Removal By An Anoxic-Aerobic Membrane Bioreactor (Mbr), Hop Phan, Faisal Ibney Hai, Jinguo Kang, Hoa Dam, Ren Zhang, William Price, Andreas Broeckmann, Long Nghiem
Faculty of Science, Medicine and Health - Papers: part A
Simultaneous nitrification/denitrification and trace organic contaminant (TrOC) removal during wastewater treatment by an integrated anoxic-aerobic MBR was examined. A set of 30 compounds was selected to represent TrOCs that occur ubiquitously in domestic wastewater. The system achieved over 95% total organic carbon (TOC) and over 80% total nitrogen (TN) removal. In addition, 21 of the 30 TrOCs investigated here were removed by over 90%. Low oxidation reduction potential (i.e., anoxic/anaerobic) regimes were conducive to moderate to high (50% to 90%) removal of nine TrOCs. These included four pharmaceuticals and personal care products (primidone, metronidazole, triclosan, and amitriptyline), one steroid hormone …
Roadblocks On The E.Coli Genome: The Workings Of A Molecular Mouse Trap At The Single-Molecule Level, Bojk A. Berghuis, David Dulin, Bronwen Cross, Nicholas Dixon, Nynke H. Dekker
Roadblocks On The E.Coli Genome: The Workings Of A Molecular Mouse Trap At The Single-Molecule Level, Bojk A. Berghuis, David Dulin, Bronwen Cross, Nicholas Dixon, Nynke H. Dekker
Faculty of Science, Medicine and Health - Papers: part A
No abstract provided.
Novel Implications Of Lingo-1 Signaling In The Post-Mortem Schizophrenia Brain, Jessica Andrews, Kelly Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Novel Implications Of Lingo-1 Signaling In The Post-Mortem Schizophrenia Brain, Jessica Andrews, Kelly Newell, Xu-Feng Huang, Francesca Fernandez-Enright
Faculty of Science, Medicine and Health - Papers: part A
Abstract of a poster that was presented at the 69th Annual Scientific Convention and Meeting of the Society of Biological Psychiatry, 8-10 May, 2014, New York city, NY.
T Cells Continue To Play On The Atp Circuit, Ronald Sluyter, Debbie Watson
T Cells Continue To Play On The Atp Circuit, Ronald Sluyter, Debbie Watson
Faculty of Science, Medicine and Health - Papers: part A
The generation of immune responses involves the coordinated communication between cells through direct cell-to-cell contact and the release of various soluble factors binding to their respective receptors. Of the many soluble factors and receptors known, there is growing evidence that the release of extracellular adenosine triphosphate (ATP) and its subsequent activation of cell-surface ligand-gated cation channels belonging to the family of P2X receptors (P2X1-7) play important roles in communication between immune cells [1]. Much of what is understood about the roles of extracellular ATP and the activation of P2X receptors during an immune response has been inferred from in vitro …
Polyunsaturated Fats, Membrane Lipids And Animal Longevity, Anthony J. Hulbert, Megan A. Kelly, Sarah K. Abbott
Polyunsaturated Fats, Membrane Lipids And Animal Longevity, Anthony J. Hulbert, Megan A. Kelly, Sarah K. Abbott
Faculty of Science, Medicine and Health - Papers: part A
Fatty acids are essential for life because they are essential components of cellular membranes. Lower animals can synthesize all four classes of fatty acids from non-lipid sources, but both omega-6 and omega-3 cannot be synthesized de novo by 'higher' animals and are therefore essential components of their diet. The relationship between normal variation in diet fatty acid composition and membrane fatty acid composition is little investigated. Studies in the rat show that, with respect to the general classes of fatty acids (saturated, monounsaturated and polyunsaturated) membrane fatty acid composition is homeostatically regulated despite diet variation. This is not the case …
Rethinking Metabotropic Glutamate Receptor 5 Pathological Findings In Psychiatric Disorders: Implications For The Future Of Novel Therapeutics, Kelly A. Newell, Natalie Matosin
Rethinking Metabotropic Glutamate Receptor 5 Pathological Findings In Psychiatric Disorders: Implications For The Future Of Novel Therapeutics, Kelly A. Newell, Natalie Matosin
Faculty of Science, Medicine and Health - Papers: part A
Background Pharmacological modulation of metabotropic glutamate receptor 5 (mGluR5) is of marked interest as a novel therapeutic mechanism to treat schizophrenia and major depression. However, the status of mGluR5 in the pathophysiology of these disorders remains unknown. Discussion The majority of studies in the schizophrenia post-mortem brain indicate that total mGluR5 expression is unaltered. However, close examination of the literature suggests that these findings are superficial, and in actuality, a number of critical factors have not yet been considered; alterations may be highly dependent on brain region, neuronal population or molecular organisation in specific cellular compartments. A number of genetic …
Intramolecular Binding Mode Of The C-Terminus Of Escherichia Coli Single-Stranded Dna Binding Protein Determined By Nuclear Magnetic Resonance Spectroscopy, Dmitry Shishmarev, Yao Wang, Claire Mason, Xun-Cheng Su, Aaron Oakley, Bim Graham, Thomas Huber, Nicholas Dixon, Gottfried Otting
Intramolecular Binding Mode Of The C-Terminus Of Escherichia Coli Single-Stranded Dna Binding Protein Determined By Nuclear Magnetic Resonance Spectroscopy, Dmitry Shishmarev, Yao Wang, Claire Mason, Xun-Cheng Su, Aaron Oakley, Bim Graham, Thomas Huber, Nicholas Dixon, Gottfried Otting
Faculty of Science, Medicine and Health - Papers: part A
Single-stranded DNA (ssDNA) binding protein (SSB) is an essential protein to protect ssDNA and recruit specific ssDNA-processing proteins. Escherichia coli SSB forms a tetramer at neutral pH, comprising a structurally well-defined ssDNA binding domain (OB-domain) and a disordered C-terminal domain (C-domain) of ∼64 amino acid residues. The C-terminal eight-residue segment of SSB (C-peptide) has been shown to interact with the OB-domain, but crystal structures failed to reveal any electron density of the C-peptide. Here we show that SSB forms a monomer at pH 3.4, which is suitable for studies by high-resolution nuclear magnetic resonance (NMR) spectroscopy. The OB-domain retains its …
Dna Replication Is The Target For The Antibacterial Effects Of Nonsteroidal Anti-Inflammatory Drugs, Zhou Yin, Yao Wang, Louise Whittell, Slobodan Jergic, Michael Liu, Elizabeth J. Harry, Nicholas Dixon, Michael Kelso, Jennifer Beck, Aaron Oakley
Dna Replication Is The Target For The Antibacterial Effects Of Nonsteroidal Anti-Inflammatory Drugs, Zhou Yin, Yao Wang, Louise Whittell, Slobodan Jergic, Michael Liu, Elizabeth J. Harry, Nicholas Dixon, Michael Kelso, Jennifer Beck, Aaron Oakley
Faculty of Science, Medicine and Health - Papers: part A
Evidence suggests that some nonsteroidal anti-inflammatory drugs (NSAIDs) possess antibacterial properties with an unknown mechanism. We describe the in vitro antibacterial properties of the NSAIDs carprofen, bromfenac, and vedaprofen, and show that these NSAIDs inhibit the Escherichia coli DNA polymerase III β subunit, an essential interaction hub that acts as a mobile tether on DNA for many essential partner proteins in DNA replication and repair. Crystal structures show that the three NSAIDs bind to the sliding clamp at a common binding site required for partner binding. Inhibition of interaction of the clamp loader and/or the replicative polymerase α subunit with …
The Structured Core Domain Of Αb-Crystallin Can Prevent Amyloid Fibrillation And Associated Toxicity, Georg K. A Hochberg, Heath Ecroyd, Cong Liu, Dezerae Cox, Duilio Cascio, Michael Sawaya, Miranda Collier, James Stroud, John A. Carver, Andrew Baldwin, Carol Robinson, David Eisenberg, Justin Benesch, Arthur Laganowsky
The Structured Core Domain Of Αb-Crystallin Can Prevent Amyloid Fibrillation And Associated Toxicity, Georg K. A Hochberg, Heath Ecroyd, Cong Liu, Dezerae Cox, Duilio Cascio, Michael Sawaya, Miranda Collier, James Stroud, John A. Carver, Andrew Baldwin, Carol Robinson, David Eisenberg, Justin Benesch, Arthur Laganowsky
Faculty of Science, Medicine and Health - Papers: part A
Mammalian small heat-shock proteins (sHSPs) are molecular chaperones that form polydisperse and dynamic complexes with target proteins, serving as a first line of defense in preventing their aggregation into either amorphous deposits or amyloid fibrils. Their apparently broad target specificity makes sHSPs attractive for investigating ways to tackle disorders of protein aggregation. The two most abundant sHSPs in human tissue are αB-crystallin (ABC) and HSP27; here we present high-resolution structures of their core domains (cABC, cHSP27), each in complex with a segment of their respective C-terminal regions. We find that both truncated proteins dimerize, and although this interface is labile …
Facile Synthesis And Preliminary Structure-Activity Analysis Of New Sulfonamides Against Trypanosoma Brucei, Adel Rashad, Amy J. Jones, Vicky M. Avery, Jonathan Baell, Paul Keller
Facile Synthesis And Preliminary Structure-Activity Analysis Of New Sulfonamides Against Trypanosoma Brucei, Adel Rashad, Amy J. Jones, Vicky M. Avery, Jonathan Baell, Paul Keller
Faculty of Science, Medicine and Health - Papers: part A
The high throughput screening of a library of over 87,000 drug-like compounds against the African sleeping sickness parasite resulted in the discovery of hits with a wide range of molecular diversity. We report here the medicinal chemistry development of one such hit, a tetrahydroisoquinoline disulfonamide, with the synthesis and testing of 26 derivatives against the trypanosome subspecies. Activities in the 2-4 μM range were revealed with a selectivity index suitable for further development.
Binding Interactions Between Nickel Schiff Base Complexes And Quadruplex Dna, Kimberley Jane Davis, Christopher Richardson, Jennifer Beck, Stephen Frederick Ralph
Binding Interactions Between Nickel Schiff Base Complexes And Quadruplex Dna, Kimberley Jane Davis, Christopher Richardson, Jennifer Beck, Stephen Frederick Ralph
Faculty of Science, Medicine and Health - Papers: part A
Abstract of a presentation that was presented at 16th International Conference on Biological Inorganic Chemistry, 22-26 July, Grenoble, France.