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Synthesis Of Some Cyclic Indolic Peptoids As Potential Antibacterials, Vicki S. Au, John B. Bremner, Jonathan Coates, Paul A. Keller, Stephen G. Pyne
Synthesis Of Some Cyclic Indolic Peptoids As Potential Antibacterials, Vicki S. Au, John B. Bremner, Jonathan Coates, Paul A. Keller, Stephen G. Pyne
Faculty of Science - Papers (Archive)
The synthesis of cyclic peptoids containing an indole hydrophobic scaffold has been realised through the ring-closing metathesis of diallylated precursors. The precursors and their cyclic counterparts possessed poor antibacterial activity in contrast to previously reported cyclic peptoids containing hydrophobic scaffolds.
The Maintenance Of High Affinity Plasminogen Binding By Group A Streptococcal Plasminogen-Binding M-Like Protein Is Mediated By Arginine And Histidine Residues Within The A1 And A2 Repeat Domains., Martina L. Sanderson-Smith, Mark J. Walker, Marie Ranson
The Maintenance Of High Affinity Plasminogen Binding By Group A Streptococcal Plasminogen-Binding M-Like Protein Is Mediated By Arginine And Histidine Residues Within The A1 And A2 Repeat Domains., Martina L. Sanderson-Smith, Mark J. Walker, Marie Ranson
Faculty of Science - Papers (Archive)
Subversion of the plasminogen activation system is implicated in the virulence of group A streptococci (GAS). GAS displays receptors for the human zymogen plasminogen on the cell surface, one of which is the plasminogen-binding group A streptococcal M-like protein (PAM). The plasminogen binding domain of PAM is highly variable, and this variation has been linked to host selective immune pressure. Site-directed mutagenesis of full-length PAM protein from an invasive GAS isolate was undertaken to assess the contribution of residues in the a1 and a2 repeat domains to plasminogen binding function. Mutagenesis to alanine of key plasminogen binding lysine residues in …
Trigger For Group A Streptococcal M1t1 Invasive Disease, J. N. Cole, Jason D. Mcarthur, F. C. Mckay, Martina L. Sanderson-Smith, Amanda J. Cork, Marie Ranson, M. Rohde, A. Itzek, H. Sun, D. Ginsburg, M. Kotb, V. Nizet, G. S. Chhatwal, Mark J. Walker
Trigger For Group A Streptococcal M1t1 Invasive Disease, J. N. Cole, Jason D. Mcarthur, F. C. Mckay, Martina L. Sanderson-Smith, Amanda J. Cork, Marie Ranson, M. Rohde, A. Itzek, H. Sun, D. Ginsburg, M. Kotb, V. Nizet, G. S. Chhatwal, Mark J. Walker
Faculty of Science - Papers (Archive)
The globally disseminated Streptococcus pyogenes M1T1 clone causes a number of highly invasive human diseases. The transition from local to systemic infection occurs by an unknown mechanism; however invasive M1T1 clinical isolates are known to express significantly less cysteine protease SpeB than M1T1 isolates from local infections. Here, we show that in comparison to the M1T1 strain 5448, the isogenic mutant ∆speB accumulated 75-fold more human plasmin activity on the bacterial surface following incubation in human plasma. Human plasminogen was an absolute requirement for M1T1 strain 5448 virulence following subcutaneous infection of humanized plasminogen transgenic mice. S. pyogenes M1T1 isolates …
The Synthesis And Testing Of Arenearylpyrimidylmethanes (Aapm) As Anti-Malarial Agents, N. R. Yepuri, R. Haritakul, R. Griffith, S. P. Leach, Paul A. Keller
The Synthesis And Testing Of Arenearylpyrimidylmethanes (Aapm) As Anti-Malarial Agents, N. R. Yepuri, R. Haritakul, R. Griffith, S. P. Leach, Paul A. Keller
Faculty of Science - Papers (Archive)
The anti-malarial activity of the arenearylpyrimidylmethane (AAPM) class of compounds emerged from database searching of a pharmacophore. A new 2 step synthesis of the AAPM scaffold is reported and subsequent substitution yielded a short synthesis of the lead anti-malarial compound. The presence of atropisomerism in this class of compounds is also reported for the first time.
Reactions Of Iminoglycines With C60 Fullerene And Their Unambiguous Characterisation Using Nmr Spectroscopy, Paul A. Keller, Stephen G. Pyne, Bill C. Hawkins
Reactions Of Iminoglycines With C60 Fullerene And Their Unambiguous Characterisation Using Nmr Spectroscopy, Paul A. Keller, Stephen G. Pyne, Bill C. Hawkins
Faculty of Science - Papers (Archive)
This review examines the addition of iminoglycine derivatives to C60, yielding protected fullerenyl pyrroline derivatives. Subsequent reduction with sodium cyanoborohydride produces ring-opening adducts which are protected fullerenyl α-amino acids. Pyrroline bisadducts can be produced using tethers to link two iminoglycine units together, and variations include combining with malonate reactive groups this giving rise to interesting observations as to the regioselectivity of such reactions. All derivatives are fully characterised by NMR spectroscopy, and in the case of bis-adducts, the regioselectivity is determined from 1H/13C and 13C/13C connectivity patterns using HMBC and INADEQUATE experiments, respectively, thus eliminating the need for comparative techniques …
The Role Of The Hpa Axis In Psychiatric Disorders And Crf Antagonists As Potential Treatments, Paul A. Keller, A. Mccluskey, J. Morgan, S. M. O'Connor
The Role Of The Hpa Axis In Psychiatric Disorders And Crf Antagonists As Potential Treatments, Paul A. Keller, A. Mccluskey, J. Morgan, S. M. O'Connor
Faculty of Science - Papers (Archive)
An overview of the links between the Hypothalamic-Pituitary-Adrenal (HPA) axis and psychiatric disorders is presented. The current treatments are outlined, indicating that they are insufficient to meet the needs of those that suffer from these affective disorders. Therefore, there is an urgent need for the generation of new therapeutics, in particular, against new targets. The association of the corticotrophin releasing factor (CRF) and the HPA axis indicates that CRF antagonists should be beneficial as potential therapeutics.
Polyamide Platinum Anti-Cancer Complexes Designed To Target Specific Dna Sequences, David Jaramillo, Nial J. Wheate, Stephen F. Ralph, Warren A. Howard, Yitzhak Tor, Janice Aldrich-Wright
Polyamide Platinum Anti-Cancer Complexes Designed To Target Specific Dna Sequences, David Jaramillo, Nial J. Wheate, Stephen F. Ralph, Warren A. Howard, Yitzhak Tor, Janice Aldrich-Wright
Faculty of Science - Papers (Archive)
Two new platinum complexes, trans-chlorodiammine[N-(2-aminoethyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-2) and trans-chlorodiammine[N-(6-aminohexyl)-4-[4-(N-methylimidazole-2-carboxamido)-N-methylpyrrole-2-carboxamido]-N-methylpyrrole-2-carboxamide]platinum(II) chloride (DJ1953-6) have been synthesized as proof-of-concept molecules in the design of agents that can specifically target genes in DNA. Coordinate covalent binding to DNA was demonstrated with electrospray ionization mass spectrometry. Using circular dichroism, these complexes were found to show greater DNA binding affinity to the target sequence: d(CATTGTCAGAC)2, than toward either d(GTCTGTCAATG)2, which contains different flanking sequences, or d(CATTGAGAGAC)2, which contains a double base pair mismatch sequence. DJ1953-2 unwinds the DNA helix by around 13°, but neither metal complex significantly affects the DNA melting temperature. Unlike simple DNA minor …
Microwave-Assisted Facile Synthesis And Crystal Structure Of Cis-9,10,11,15-Tetrahydro-9,10[3'4']-Furanoanthracene-12,14-Dione, Weerachai Phutdhawong, Duang Buddhasukh, Stephen G. Pyne, Apinpus Rujiwatra, Chaveng Pakawatchai
Microwave-Assisted Facile Synthesis And Crystal Structure Of Cis-9,10,11,15-Tetrahydro-9,10[3'4']-Furanoanthracene-12,14-Dione, Weerachai Phutdhawong, Duang Buddhasukh, Stephen G. Pyne, Apinpus Rujiwatra, Chaveng Pakawatchai
Faculty of Science - Papers (Archive)
A facile synthesis and crystal structure of cis‐9,10,11,15‐tetrahydro‐9,10[3′,4′]‐furanoanthracene‐12,14‐dione from the reaction of anthracene and maleic anhydride in xylene in a short time and high yield using a modified commercial domestic microwave oven is reported.
Development Of Robust Guidelines And Assessment Procedures For Metal Contaminated Sediments, David Strom, Stuart L. Simpson, Dianne F. Jolley
Development Of Robust Guidelines And Assessment Procedures For Metal Contaminated Sediments, David Strom, Stuart L. Simpson, Dianne F. Jolley
Faculty of Science - Papers (Archive)
Assessment of contaminated sediments and development of remediation strategies is becoming an important priority for regulators and industries worldwide. Although sediment quality assessment frameworks exist, poor scientific procedures and a limited understanding of species sensitivity to common contaminants hinders most assessment programs. Globally, sediment quality guidelines (SQGs) for metals vary over several orders of magnitude and are not based on clear cause-effect relationships. Although equilibrium partitioning approaches to developing SQGs have been attempted, the cause-effect relationships are weak due to the many other modifying factors that influence metal bioavailability and toxicity. The inherent lack of defensible SQGs for metals currently …
Dichlorobis(2,5-Diphenyl-1,3,4-ThiaâDiazole-κn3)Palladium(Ii), Peter Steel, Christopher Richardson
Dichlorobis(2,5-Diphenyl-1,3,4-ThiaâDiazole-κn3)Palladium(Ii), Peter Steel, Christopher Richardson
Faculty of Science - Papers (Archive)
The title complex, [PdCl2(C14H10N2S)2], crystallizes with two half-molecules in the asymmetric unit which have significantly different conformations of the aromatic rings of the coordinated ligands. The molecules are centrosymmetric.
Novel Polycyclic Diels-Alder Adducts From Ring Distorted 3-Aza[5] And 3-Aza[6] (1,7) Napthalenophanes, John B. Bremner, Wasna Jaturonusmee
Novel Polycyclic Diels-Alder Adducts From Ring Distorted 3-Aza[5] And 3-Aza[6] (1,7) Napthalenophanes, John B. Bremner, Wasna Jaturonusmee
Faculty of Science - Papers (Archive)
Ring distorted 3-aza[5] and 3-aza[6](1,7)naphthalenophanes have been shown to undergo ready Diels-Alder cycloaddition reactions with 4-phenyl-1,2,4-triazoline-3,5-dione, tetracyanoethylene, 1,1-dicyanoethylene and 1,1-diethyl methylenemalonate to form new functionalized polycyclic heterocyclic derivatives. Addition was shown to occur selectively in each case in the less substituted aromatic ring of the naphthalene moiety.
Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis
Synthesis And In Vitro Binding Of N,N-Dialkyl-2-Phenylindol-3-Ylglyoxylamides For The Peripheral Benzodiazepine Binding Sites, T. P. Homes, F. Mattner, Paul A. Keller, A. Katsifis
Faculty of Science - Papers (Archive)
A series of N,N-dialkyl-2-phenylindol-3-ylglyoxylamides bearing the halogens iodine and bromine were synthesised and their binding affinity for the peripheral benzodiazepine binding sites (PBBS) in rat kidney mitochondrial membranes were evaluated using [3H]-PK11195. Central benzodiazepine receptor (CBR) affinities were also evaluated in rat cortices using 3H-flumazenil to determine their selectivity for PBBS over CBR. The tested compounds had PBBS binding affinities (IC50) ranging from 7.86 nM to 618 nM, with all compounds showing high selectivity over the CBR (CBR IC50 > 5000 nM). Among the 12 compounds tested, those with a diethylamide group were the most potent. The highest affinity iodinated PBBS …
An Epididymal Form Of Cauxin, A Carboxylesterase-Like Enzyme, Is Present And Active In Mammalian Male Reproductive Fluids, Heath W. Ecroyd, Maya Belghazi, Jl Dacheux, M Miyazaki, T Yamashita, Jl Gatti
An Epididymal Form Of Cauxin, A Carboxylesterase-Like Enzyme, Is Present And Active In Mammalian Male Reproductive Fluids, Heath W. Ecroyd, Maya Belghazi, Jl Dacheux, M Miyazaki, T Yamashita, Jl Gatti
Faculty of Science - Papers (Archive)
Mass spectrometric analysis of a prion protein (PrP)-containing complex isolated from ram cauda epididymal fluid revealed a protein that showed homology to a carboxylesterase-like protein previously identified in cat urine (cauxin). Using anticauxin antibodies, immunoreactive bands were detected in corpus and cauda epididymal fluid from all mammals tested (ram, boar, mouse, and cat). In the ram, the protein was also present in seminal fluid but not found to be associated with sperm. The bands reacting with the anti-cauxin antibody coincided with those having esterase activity in a zymographic assay and its levels paralleled the esterase activity of native epididymal fluids. …
Proteomic Dissection Of Dna Polymerization, Jennifer L. Beck, Thitima Urathamakul, Stephen James Watt, Margaret Sheil, Patrick M. Schaeffer, Nicholas E. Dixon
Proteomic Dissection Of Dna Polymerization, Jennifer L. Beck, Thitima Urathamakul, Stephen James Watt, Margaret Sheil, Patrick M. Schaeffer, Nicholas E. Dixon
Faculty of Science - Papers (Archive)
DNA polymerases replicate the genome by associating with a range of other proteins that enable rapid, high-fidelity copying of DNA. This complex of proteins and nucleic acids is called the replisome. Proteins of the replisome must interact with other networks of proteins, such as those involved in DNA repair. Many of the proteins involved in DNA polymerisation and the accessory proteins are known, but the array of proteins they interact with, and the spatial and temporal arrangement of these interactions is a current research topic. Mass spectrometry is a technique that can be used to identify the sites of these …
Evidence From Mitochondrial Genomics On Interordinal Relationships In Insects, Stephen L. Cameron, Andrew T. Beckenbach, Mark P. Dowton, Michael F. Whiting
Evidence From Mitochondrial Genomics On Interordinal Relationships In Insects, Stephen L. Cameron, Andrew T. Beckenbach, Mark P. Dowton, Michael F. Whiting
Faculty of Science - Papers (Archive)
No abstract provided.
Asymmetric Synthesis Of Anti-1,2-Amino Alcohols Via The Borono-Mannich Reaction: A Formal Synthesis Of (-)-Swainsonine, Christopher W. G. Au, Stephen G. Pyne
Asymmetric Synthesis Of Anti-1,2-Amino Alcohols Via The Borono-Mannich Reaction: A Formal Synthesis Of (-)-Swainsonine, Christopher W. G. Au, Stephen G. Pyne
Faculty of Science - Papers (Archive)
Chiral α-hydroxy-aldehydes generated in situ by the ADH reaction of vinyl sulfones undergo a borono-Mannich reaction with β-styrenyl boronic acid and primary amines to give anti-1,2-amino alcohols in high enantiomeric purities (ee 83-95%). This new method allows much more rapid access to these valuable chiral building blocks that has been used in a short formal synthesis (10 synthetic steps from 4-penten-1-ol) of (-)-swainsonine.
Structure Of The Theta Subunit Of Escherichia Coli Dna Polymerase Iii In Complex With The Epsilon Subunit, Max A Keniry, Ah-Young Park, Elisabeth A. Owen, Samir M. Hamdan, Guido Pintacuda, Gottfried Otting, Nicholas E. Dixon
Structure Of The Theta Subunit Of Escherichia Coli Dna Polymerase Iii In Complex With The Epsilon Subunit, Max A Keniry, Ah-Young Park, Elisabeth A. Owen, Samir M. Hamdan, Guido Pintacuda, Gottfried Otting, Nicholas E. Dixon
Faculty of Science, Medicine and Health - Papers: part A
The catalytic core of Escherichia coli DNA polymerase III contains three tightly associated subunits, the α, ε, and θ subunits. The θ subunit is the smallest and least understood subunit. The three-dimensional structure of θ in a complex with the unlabeled N-terminal domain of the ε subunit, ε186, was determined by multidimensional nuclear magnetic resonance spectroscopy. The structure was refined using pseudocontact shifts that resulted from inserting a lanthanide ion (Dy3+, Er3+, or Ho3+) at the active site of ε186. The structure determination revealed a three-helix bundle fold that is similar to the solution …
Domains Of Group A Streptococcal M Protein That Confer Resistance To Phagocytosis, Opsonization And Protection: Implications For Vaccine Development., Jason D. Mcarthur, Mark J. Walker
Domains Of Group A Streptococcal M Protein That Confer Resistance To Phagocytosis, Opsonization And Protection: Implications For Vaccine Development., Jason D. Mcarthur, Mark J. Walker
Faculty of Science - Papers (Archive)
Streptococcus pyogenes (group A streptococcus) colonises skin and throat tissues resulting in a range of benign and serious human diseases. Opsonisation and phagocytosis are important defence mechanisms employed by the host to destroy group A streptococci. Antisera against the cell-surface M protein, of which over 150 different types have been identified, are opsonic and contribute to disease protection . In this issue of Molecular Microbiology, Sandin and colleagues have comprehensively analysed the regions of M5 protein that contribute to phagocytosis resistance and opsonisation. Human plasma proteins bound to M5 protein B- and C-repeats were shown to block opsonisation, an observation …
Application Of Surrogate Methods For Assessing The Bioavailability Of Pahs In Sediments To A Sediment Ingesting Bivalve, Stuart L. Simpson, Victoria L. Burston, Dianne F. Jolley, Kim Chau
Application Of Surrogate Methods For Assessing The Bioavailability Of Pahs In Sediments To A Sediment Ingesting Bivalve, Stuart L. Simpson, Victoria L. Burston, Dianne F. Jolley, Kim Chau
Faculty of Science - Papers (Archive)
The usefulness of two surrogate methods for rapidly determining the bioavailability of PAHs in hydrocarbon-contaminated marine sediments was assessed. Comparisons are made between the PAHs accumulated by the benthic bivalve, Tellina deltoidalis, and the extractable-PAHs determined using a 6-h XAD-2 resin desorption method and a 4-h gut fluid mimic (GFM) extraction method. There were significant positive relationships between PAH bioaccumulation by the bivalves and sediment PAH concentrations. These relationships were not improved by normalising the sediment PAH concentrations to the organic carbon concentration. The average percentage lipid content of the bivalves was 1.47 ± 0.22% and BSAFs for total-PAHs ranged …
Tandem Mass Spectrometry Reveals The Quaternary Organization Of Macromolecular Assemblies, J L Benesch, Andrew Aquilina, Brandon T. Ruotolo, Frank Sobott, C V Robinson
Tandem Mass Spectrometry Reveals The Quaternary Organization Of Macromolecular Assemblies, J L Benesch, Andrew Aquilina, Brandon T. Ruotolo, Frank Sobott, C V Robinson
Faculty of Science - Papers (Archive)
The application of mass spectrometry (MS) to the study of progressively larger and more complex macromolecular assemblies is proving increasingly useful for structural biologists. The scope of this approach has recently been widened through the application of a tandem MS procedure. This two-step technique involves the selection of specific assemblies in the gas phase, and inducing their dissociation through collisions with argon atoms. Here we investigate the mechanism of this process and show that dissociation of subunits from a macromolecular assembly follows a sequential pathway, with the partitioning of charge between the dissociation products governed primarily by their relative surface …
Helicase-Binding To Dnai Exposes A Cryptic Dna-Binding Site During Helicase Loading In Bacillus Subtilis, Charikleia Ioannou, Patrick M. Schaeffer, Nicholas E. Dixon, Panos Soultanas
Helicase-Binding To Dnai Exposes A Cryptic Dna-Binding Site During Helicase Loading In Bacillus Subtilis, Charikleia Ioannou, Patrick M. Schaeffer, Nicholas E. Dixon, Panos Soultanas
Faculty of Science - Papers (Archive)
The Bacillus subtilis DnaI, DnaB and DnaD proteins load the replicative ring helicase DnaC onto DNA during priming of DNA replication. Here we show that DnaI consists of a C-terminal domain (Cd) with ATPase and DNA-binding activities and an N-terminal domain (Nd) that interacts with the replicative ring helicase. A Zn21-binding module mediates the interaction with the helicase and C67, C70 and H84 are involved in the coordination of the Zn21. DnaI binds ATP and exhibits ATPase activity that is not stimulated by ssDNA, because the DNAbinding site on Cd is masked by Nd. The ATPase activity resides on the …
Identification Of The Rest Regulon Reveals Extensive Transposable Element-Mediated Binding Site Duplication, Rory Johnson, Richard J. Gamblin, Lezanne Ooi, Alexander W. Bruce, Ian J. Donaldson, David R. Westhead, Ian Wood, Richard M. Jackson, Noel J. Buckley
Identification Of The Rest Regulon Reveals Extensive Transposable Element-Mediated Binding Site Duplication, Rory Johnson, Richard J. Gamblin, Lezanne Ooi, Alexander W. Bruce, Ian J. Donaldson, David R. Westhead, Ian Wood, Richard M. Jackson, Noel J. Buckley
Faculty of Science - Papers (Archive)
The genome-wide mapping of gene-regulatory motifs remains a major goal that will facilitate the modelling of gene-regulatory networks and their evolution. The repressor element 1 is a long, conserved transcription factor-binding site which recruits the transcriptional repressor REST to numerous neuron-specific target genes. REST plays important roles in multiple biological processes and disease states. To map RE1 sites and target genes, we created a position specific scoring matrix representing the RE1 and used it to search the human and mouse genomes. We identified 1301 and 997 RE1s inhuman and mouse genomes, respectively, of which >40% are novel. By employing an …
Comparison Of Virulence Gene Profiles Between Escherichia Coli Strains Isolated From Healthy And Diarrheic Swine, Mark R. Wilson, Xi Yang Wu, Idris Barchia, Karl A Bettelheim, Steven Driesen, Darren J. Trott, Toni A. Chapman, James J C Chin
Comparison Of Virulence Gene Profiles Between Escherichia Coli Strains Isolated From Healthy And Diarrheic Swine, Mark R. Wilson, Xi Yang Wu, Idris Barchia, Karl A Bettelheim, Steven Driesen, Darren J. Trott, Toni A. Chapman, James J C Chin
Faculty of Science - Papers (Archive)
A combination of uni- and multiplex PCR assays targeting 58 virulence genes (VGs) associated with Escherichia coli strains causing intestinal and extraintestinal disease in humans and other mammals was used to analyze the VG repertoire of 23 commensal E. coli isolates from healthy pigs and 52 clinical isolates associated with porcine neonatal diarrhea (ND) and postweaning diarrhea (PWD). The relationship between the presence and absence of VGs was interrogated using three statistical methods. According to the generalized linear model, 17 of 58 VGs were found to be significant (P < 0.05) in distinguishing between commensal and clinical isolates. Nine of the 17 genes represented by iha, hlyA, aidA, east1, aah, fimH, iroN(E. coli), traT, and saa have not been previously identified as important VGs in clinical porcine isolates in Australia. The remaining eight VGs code for fimbriae (F4, F5, F18, and F41) and toxins (STa, STb, LT, and Stx2), normally associated with porcine enterotoxigenic E. coli. Agglomerative hierarchical algorithm analysis grouped E. coli strains into subclusters based primarily on their serogroup. Multivariate analyses of clonal relationships based on the 17 VGs were collapsed into two-dimensional space by principal coordinate analysis. PWD clones were distributed in two quadrants, separated from ND and commensal clones, which tended to cluster within one quadrant. Clonal subclusters within quadrants were highly correlated with serogroups. These methods of analysis provide different perspectives in our attempts to understand how commensal and clinical porcine enterotoxigenic E. coli strains have evolved and are engaged in the dynamic process of losing or acquiring VGs within the pig population.