%0 Journal Article
%~ PubMed
%A Liao, Vivian
%A Liu, Tao
%A Codd, Rachel
%T Amide-based derivatives of β-alanine hydroxamic acid as histone deacetylase inhibitors: Attenuation of potency through resonance effects.
%B Bioorganic & Medicinal Chemistry Letters
%D 2012
%C United Kingdom
%I Pergamon
%V 22
%N 19
%P 6200-6204
%@ 1464-3405
%X A library of amide-linked derivatives of ??-alanine hydroxamic acid were prepared (2-7) and the activity as inhibitors of Zn(II)-containing histone deacetylases (HDACs) determined in vitro against HDAC1 and the anti-proliferative activity determined in BE(2)-C neuroblastoma cells. The IC(50) values of the best-performing compounds (3-7) against HDAC1 ranged between 38 and 84??M. The least potent compound (2) inhibited a maximum of only 40% HDAC1 activity at 250??M. The anti-proliferative activity of 2-7 at 50??M against BE(2)-C neuroblastoma cells ranged between 57.0% and 88.6%. The structural similarity between the potent HDAC inhibitor trichostatin A (TSA, 1; HDAC1, IC(50) 12nM) and the present compounds (2-7) was high at the Zn(II) coordinating hydroxamic acid head group; and in selected compounds (2, 5), at the 4-(dimethylamino)phenyl tail. The significantly reduced potency of 2-7 relative to 1 underscores the rank importance of the linker region as part of the HDAC inhibitor pharmacophore. Molecular modeling of 1-7 using HDAC8 as the template suggested that the conformationally constrained 4''-methyl group of 1 may contribute to HDAC inhibitor potency through a sandwich-like interaction with a hydrophobic region containing F152 and F208; and that the absence of this group in 2-7 may reduce potency. The close proximity of the 5''-carbonyl oxygen atom in 2-7 to the sulfur atom of Met274 in HDAC8 or the corresponding isobutyl group of Leu274 in HDAC1 may attenuate potency through repulsive steric and dipole-dipole forces. In a unique resonance stabilized form of 2, this interaction could manifest as stronger ion-dipole repulsive forces, resulting in a further decrease in potency. This work suggests that resonance structures of HDAC inhibitors could modulate intermolecular interactions with HDAC targets, and potency.
%Z FOR Codes: 30402 111205


%0 Journal Article
%A Ejje, Najwa
%A Lacey, Ernest
%A Codd, Rachel
%T Analytical-scale purification of trichostatin A from bacterial culture in a single step and with high selectivity using immobilised metal affinity chromatography
%B RSC Advances
%D 2012
%C United Kingdom
%I The Royal Society of Chemistry
%V 2
%N 1
%P 333-337
%@ 2046-2069
%X 
%Z FOR Codes: 111501


%0 Journal Article
%~ PubMed
%A Lifa, Tulip
%A Ejje, Najwa
%A Codd, Rachel
%T Coordinate-bond-dependent solid-phase organic synthesis of biotinylated desferrioxamine B: a new route for metal-specific probes.
%B Chemical Communications
%D 2012
%C United Kingdom
%I Royal Society of Chemistry
%V 48
%N 14
%P 2003-2005
%@ 1364-548X
%X Desferrioxamine B (DFOB) was biotinylated at the pendant amine using solid-phase organic synthesis (SPOS) on a matrix used conventionally for metal affinity chromatography. The strength of the DFOB-matrix coordinate bonds was functionally equivalent to a covalent bond which underpinned the veracity of the SPOS format. After washing excess reagents, biotin-DFOB was eluted from the matrix with water at pH 6.
%Z FOR Codes: 30401 30201 100402


%0 Journal Article
%~ PubMed
%A Gu, Jiesi
%A Codd, Rachel
%T Copper(II)-based metal affinity chromatography for the isolation of the anticancer agent bleomycin from Streptomyces verticillus culture.
%B Journal of Inorganic Biochemistry
%D 2012
%C United States
%I Elsevier Inc.
%V 115
%N 
%P 198-203
%@ 0162-0134
%X 
%Z FOR Codes: 30401 30201


%0 Journal Article
%~ PubMed
%A Soe, Cho Z
%A Pakchung, Amalie A H
%A Codd, Rachel
%T Directing the Biosynthesis of Putrebactin or Desferrioxamine B in Shewanella putrefaciens through the Upstream Inhibition of Ornithine Decarboxylase.
%B Chemistry & Biodiversity
%D 2012
%C Germany
%I Wiley - V C H Verlag GmbH & Co. KGaA
%V 9
%N 9
%P 1880-1890
%@ 1612-1880
%X 
%Z FOR Codes: 30201 60113 30402


%0 Journal Article
%~ PubMed
%A Hare, Nathan J
%A Soe, Cho Zin
%A Rose, Barbara
%A Harbour, Colin
%A Codd, Rachel
%A Manos, Jim
%A Cordwell, Stuart J
%T Proteomics of <i>Pseudomonas aeruginosa</i> Australian epidemic strain 1 (AES-1) cultured under conditions mimicking the cystic fibrosis lung reveals increased iron acquisition via the siderophore pyochelin.
%B Journal of proteome research
%D 2012
%C United States
%I American Chemical Society
%V 11
%N 2
%P 776-95
%@ 1535-3893
%X Pseudomonas aeruginosa is an opportunistic pathogen that is the major cause of morbidity and mortality in patients with cystic fibrosis (CF). While most CF patients are thought to acquire P. aeruginosa from the environment, person-to-person transmissible strains have been identified in CF clinics worldwide, and the molecular basis for transmissibility remains poorly understood. We undertook a complementary proteomics approach to characterize protein profiles from a transmissible, acute isolate of the Australian epidemic strain 1 (AES-1R), the virulent burns/wound isolate PA14, and the poorly virulent, laboratory-associated strain PAO1 when grown in an artificial medium that mimics the CF lung environment compared to growth in standard laboratory medium. Proteins elevated in abundance in AES-1R included those involved in methionine and S-adenosylmethionine biosynthesis and in the synthesis of phenazines. Proteomic data were validated by measuring culture supernatant levels of the virulence factor pyocyanin, which is the final product of the phenazine pathway. AES-1R and PAO1 released higher extracellular levels of pyocyanin compared to PA14 when grown in conditions that mimic the CF lung. Proteins associated with biosynthesis of the iron-scavenging siderophore pyochelin (PchDEFGH and FptA) were also present at elevated abundance in AES-1R and at much higher levels than in PAO1, whereas they were reduced in PA14. These protein changes resulted phenotypically in increased extracellular iron acquisition potential and, specifically, elevated pyochelin levels in AES-1R culture supernatants as detected by chrome azurol-S assay and fluorometry, respectively. Transcript analysis of pyochelin genes (pchDFG and fptA) showed they were highly expressed during the early stage of growth in artificial sputum medium (18 h) but returned to basal levels following the establishment of microcolony growth (72 h) consistent with that observed in the CF lung. This provides further evidence that iron acquisition by pyochelin may play a role in the early stages of transmissible CF infection associated with AES-1R.
%Z FOR Codes: 30406 110801 60109


%0 Journal Article
%~ PubMed
%A Simpson, Philippa J L
%A Codd, Rachel
%T Cold adaptation of the mononuclear molybdoenzyme periplasmic nitrate reductase from the Antarctic bacterium Shewanella gelidimarina.
%B Biochemical and biophysical research communications
%D 2011
%C United States
%I Academic Press
%V 414
%N 4
%P 783-8
%@ 0006-291X
%X The reduction of nitrate to nitrite is catalysed in bacteria by periplasmic nitrate reductase (Nap) which describes a system of variable protein subunits encoded by the nap operon. Nitrate reduction occurs in the NapA subunit, which contains a bis-molybdopterin guanine dinucleotide (Mo-MGD) cofactor and one [4Fe-4S] iron-sulfur cluster. The activity of periplasmic nitrate reductase (Nap) isolated as native protein from the cold-adapted (psychrophilic) Antarctic bacterium Shewanella gelidimarina (Nap(Sgel)) and middle-temperature adapted (mesophilic) Shewanella putrefaciens (Nap(Sput)) was examined at varied temperature. Irreversible deactivation of Nap(Sgel) and Nap(Sput) occurred at 54.5 and 65??C, respectively. When Nap(Sgel) was preincubated at 21-70??C for 30 min, the room-temperature nitrate reductase activity was maximal and invariant between 21 and 54??C, which suggested that Nap(Sgel) was poised for optimal catalysis at modest temperatures and, unlike Nap(Sput), did not benefit from thermally-induced refolding. At 20??C, Nap(Sgel) reduced selenate at 16% of the rate of nitrate reduction. Nap(Sput) did not reduce selenate. Sequence alignment showed 46 amino acid residue substitutions in Nap(Sgel) that were conserved in NapA from mesophilic Shewanella, Rhodobacter and Escherichia species and could be associated with the Nap(Sgel) cold-adapted phenotype. Protein homology modeling of Nap(Sgel) using a mesophilic template with 66% amino acid identity showed the majority of substitutions occurred at the protein surface distal to the Mo-MGD cofactor. Two mesophilic???psychrophilic substitutions (Asn???His, Val???Trp) occurred in a region close to the surface of the NapA substrate funnel resulting in potential interdomain ??-?? and/or cation-?? interactions. Three mesophilic???psychrophilic substitutions occurred within 4.5?? of the Mo-MGD cofactor (Phe???Met, Ala???Ser, Ser???Thr) resulting in local regions that varied in hydrophobicity and hydrogen bonding networks. These results contribute to the understanding of thermal protein adaptation in a redox-active mononuclear molybdenum enzyme and have implications in optimizing the design of low-temperature environmental biosensors.
%Z FOR Codes: 60107 60102 60114


%0 Journal Article
%~ PubMed
%A Groebler, Ludwig K
%A Liu, Joe
%A Shanu, Anu
%A Codd, Rachel
%A Witting, Paul K
%T Comparing the potential renal protective activity of desferrioxamine B and the novel chelator desferrioxamine B-N-(3-hydroxyadamant-1-yl)carboxamide in a cell model of myoglobinuria.
%B The Biochemical Journal
%D 2011
%C United States
%I Portland Press Ltd.
%V 435
%N 3
%P 669-677
%@ 1470-8728
%X Accumulating Mb (myoglobin) in the kidney following severe burns promotes oxidative damage and inflammation, which leads to acute renal failure. The potential for haem-iron to induce oxidative damage has prompted testing of iron chelators [e.g. DFOB (desferrioxamine B)] as renal protective agents. We compared the ability of DFOB and a DFOB-derivative {DFOB-AdAOH [DFOB-N-(3-hydroxyadamant-1-yl)carboxamide]} to protect renal epithelial cells from Mb insult. Loading kidney-tubule epithelial cells with dihydrorhodamine-123 before exposure to 100????M Mb increased rhodamine-123 fluorescence relative to controls (absence of Mb), indicating increased oxidative stress. Extracellular Mb elicited a reorganization of the transferrin receptor as assessed by monitoring labelled transferrin uptake with flow cytometry and inverted fluorescence microscopy. Mb stimulated HO-1 (haem oxygenase-1), TNF?? (tumour necrosis factor ??), and both ICAM (intercellular adhesion molecule) and VCAM (vascular cell adhesion molecule) gene expression and inhibited epithelial monolayer permeability. Pre-treatment with DFOB or DFOB-AdAOH decreased Mb-mediated rhodamine-123 fluorescence, HO-1, ICAM and TNF?? gene expression and restored monolayer permeability. MCP-1 (monocyte chemotactic protein 1) secretion increased in cells exposed to Mb-insult and this was abrogated by DFOB or DFOB-AdAOH. Cells treated with DFOB or DFOB-AdAOH alone showed no change in permeability, MCP-1 secretion or HO-1, TNF??, ICAM or VCAM gene expression. Similarly to DFOB, incubation of DFOB-AdAOH with Mb plus H2O2 yielded nitroxide radicals as detected by EPR spectroscopy, indicating a potential antioxidant activity in addition to metal chelation; Fe(III)-loaded DFOB-AdAOH showed no nitroxide radical formation. Overall, the chelators inhibited Mb-induced oxidative stress and inflammation and improved epithelial cell function. DFOB-AdAOH showed similar activity to DFOB, indicating that this novel low-toxicity chelator may protect the kidney after severe burns.
%Z FOR Codes: 30401


%0 Journal Article
%~ PubMed
%A Pakchung, Amalie A H
%A Soe, Cho Zin
%A Lifa, Tulip
%A Codd, Rachel
%T Complexes Formed in Solution Between Vanadium(IV)/(V) and the Cyclic Dihydroxamic Acid Putrebactin or Linear Suberodihydroxamic Acid.
%B Inorganic chemistry
%D 2011
%C United States
%I American Chemical Society
%V 50
%N 13
%P 5978-89
%@ 0020-1669
%X An aerobic solution prepared from V(IV) and the cyclic dihydroxamic acid putrebactin (pbH(2)) in 1:1 H(2)O/CH(3)OH at pH = 2 turned from blue to orange and gave a signal in the positive ion electrospray ionization mass spectrometry (ESI-MS) at m/z(obs) 437.0 attributed to the monooxoV(V) species [V(V)O(pb)](+) ([C(16)H(26)N(4)O(7)V](+), m/z(calc) 437.3). A solution prepared as above gave a signal in the (51)V NMR spectrum at ??(V )= -443.3 ppm (VOCl(3), ??(V) = 0 ppm) and was electron paramagnetic resonance silent, consistent with the presence of [V(V)O(pb)](+). The formation of [V(V)O(pb)](+) was invariant of [V(IV)]:[pbH(2)] and of pH values over pH = 2-7. In contrast, an aerobic solution prepared from V(IV) and the linear dihydroxamic acid suberodihydroxamic acid (sbhaH(4)) in 1:1 H(2)O/CH(3)OH at pH values of 2, 5, or 7 gave multiple signals in the positive and negative ion ESI-MS, which were assigned to monomeric or dimeric V(V)- or V(IV)-sbhaH(4) complexes or mixed-valence V(V)/(IV)-sbhaH(4) complexes. The complexity of the V-sbhaH(4) system has been attributed to dimerization (2[V(V)O(sbhaH(2))](+) ??? [(V(V)O)(2)(sbhaH(2))(2)](2+)), deprotonation ([V(V)O(sbhaH(2))](+) - H(+) ??? [V(V)O(sbhaH)](0)), and oxidation ([V(IV)O(sbhaH(2))](0) -e(-) ??? [V(V)O(sbhaH(2))](+)) phenomena and could be described as the sum of two pH-dependent vectors, the first comprising the deprotonation of hydroxamate (low pH) to hydroximate (high pH) and the second comprising the oxidation of V(IV) (low pH) to V(V) (high pH). Macrocyclic pbH(2) was preorganized to form [V(V)O(pb)](+), which would provide an entropy-based increase in its thermodynamic stability compared to V(V)-sbhaH(4) complexes. The half-wave potentials from solutions of [V(IV)]:[pbH(2)] (1:1) or [V(IV)]:[sbhaH(4)] (1:2) at pH = 2 were E(1/2) -335 or -352 mV, respectively, which differed from the expected trend (E(1/2) [VO(pb)](+/0) < V(V/IV)-sbhaH(4)). The complex solution speciation of the V(V)/(IV)-sbhaH(4) system prevented the determination of half-wave potentials for single species. The characterization of [V(V)O(pb)](+) expands the small family of documented V-siderophore complexes relevant to understanding V transport and assimilation in the biosphere.
%Z FOR Codes: 302


%0 Journal Article
%~ PubMed
%A Liu, Joe
%A Obando, Daniel
%A Liao, Vivian
%A Lifa, Tulip
%A Codd, Rachel
%T The many faces of the adamantyl group in drug design.
%B European journal of medicinal chemistry
%D 2011
%C France
%I Elsevier Masson
%V 46
%N 6
%P 1949-63
%@ 1768-3254
%X Adamantyl-based compounds are used clinically for the treatment of neurological conditions, as anti-viral agents and as agents against type 2 diabetes. The value of the adamantyl group in drug design is multidimensional. The hydrophobic substituent constant for the adamantyl group has been estimated from the calculated partition coefficients (clogP values) of 31 adamantyl-bearing compounds in the clinic or in development as ??adamantyl=3.1, which indicates that the logP value of a compound with high water solubility (logP<0) could be moved with an adamantyl-based modification to a region that is more clinically useful. The steric bulk of the adamantyl group can: (i) restrict or modulate intramolecular reactivity; and (ii) impede the access of hydrolytic enzymes, thereby increasing drug stability and plasma half life. The value of the adamantyl group in drug design has been recognized most recently in the design of agents to treat iron overload disease (in development), malaria (in clinical trials) and type 2 diabetes (in the clinic).
%Z FOR Codes: 30402 30404


%0 Journal Article
%~ PubMed
%A Wubben, Jacinta M
%A Dogovski, Con
%A Dobson, Renwick C J
%A Codd, Rachel
%A Gerrard, Juliet A
%A Parker, Michael W
%A Perugini, Matthew A
%T Cloning, expression, purification and crystallization of dihydrodipicolinate synthase from the psychrophile Shewanella benthica.
%B Acta Crystallographica. Section F: Structural Biology and Crystallization Communications
%D 2010
%C United States, Unite
%I Wiley-Blackwell Publishing, Inc.
%V 66
%N Pt 11
%P 1511-1516
%@ 1744-3091
%X Dihydrodipicolinate synthase (DHDPS) is an oligomeric enzyme that catalyzes the first committed step of the lysine-biosynthesis pathway in plants and bacteria, which yields essential building blocks for cell-wall and protein synthesis. DHDPS is therefore of interest to drug-discovery research as well as to studies that probe the importance of quaternary structure to protein function, stability and dynamics. Accordingly, DHDPS from the psychrophilic (cold-dwelling) organism Shewanella benthica (Sb-DHDPS) was cloned, expressed, purified and crystallized. The best crystals of Sb-DHDPS were grown in 200?mM ammonium sulfate, 100?mM bis-tris pH 5.0-6.0, 23-26%(w/v) PEG 3350, 0.02%(w/v) sodium azide and diffracted to beyond 2.5?Å resolution. Processing of diffraction data to 2.5?Å resolution resulted in a unit cell with space group P2(1)2(1)2(1) and dimensions a = 73.1, b = 84.0, c = 143.7?Å. These studies of the first DHDPS enzyme to be characterized from a bacterial psychrophile will provide insight into the molecular evolution of enzyme structure and dynamics.
%Z FOR Codes: 60106


%0 Journal Article
%~ PubMed
%A Liu, Joe
%A Obando, Daniel
%A Schipanski, Liam G
%A Groebler, Ludwig K
%A Witting, Paul K
%A Kalinowski, Danuta S
%A Richardson, Des R
%A Codd, Rachel
%T Conjugates of Desferrioxamine B (DFOB) with Derivatives of Adamantane or with Orally Available Chelators as Potential Agents for Treating Iron Overload.
%B Journal of medicinal chemistry
%D 2010
%C United States
%I American Chemical Society
%V 53
%N 3
%P 1370-82
%@ 0022-2623
%X Desferrioxamine B (DFOB) conjugates with adamantane-1-carboxylic acid, 3-hydroxyadamantane-1-carboxylic acid, 3,5-dimethyladamantane-1-carboxylic acid, adamantane-1-acetic acid, 4-methylphenoxyacetic acid, 3-hydroxy-2-methyl-4-oxo-1-pyridineacetic acid (N-acetic acid derivative of deferiprone), or 4-[3,5-bis(2-hydroxyphenyl)-1,2,4-triazol-1-yl]benzoic acid (deferasirox) were prepared and the integrity of Fe(III) binding of the compounds was established from electrospray ionization mass spectrometry and RP-HPLC measurements. The extent of intracellular (59)Fe mobilized by the DFOB-3,5-dimethyladamantane-1-carboxylic acid adduct was 3-fold greater than DFOB alone, and the IC(50) value of this adduct was 6- or 15-fold greater than DFOB in two different cell types. The relationship between logP and (59)Fe mobilization for the DFOB conjugates showed that maximal mobilization of intracellular (59)Fe occurred at a logP value approximately 2.3. This parameter, rather than the affinity for Fe(III), appears to influence the extent of intracellular (59)Fe mobilization. The low toxicity-high Fe mobilization efficacy of selected adamantane-based DFOB conjugates underscores the potential of these compounds to treat iron overload disease in patients with transfusional-dependent disorders such as beta-thalassemia.
%Z FOR Codes: 30405 30404 110103


%0 Journal Article
%~ PubMed
%A Simpson, Philippa J L
%A McKinzie, Audra A
%A Codd, Rachel
%T Resolution of two native monomeric 90 kDa nitrate reductase active proteins from Shewanella gelidimarina and the sequence of two napA genes.
%B Biochemical and biophysical research communications
%D 2010
%C United States
%I Academic Press
%V 398
%N 1
%P 13-8
%@ 0006-291X
%X The reduction of nitrate to nitrite in the bacterial periplasm occurs in the 90kDa NapA subunit of the periplasmic nitrate reductase (NAP) system. Most Shewanella genomes contain two nap operons: napEDABC and napDAGHB, which is an unusual feature of this genus. Two native, monomeric, 90kDa nitrate reductase active proteins were resolved by hydrophobic interaction chromatography from aerobic cultures of Shewanella gelidimarina replete with reduced nitrogen compounds. The 90kDa protein obtained in higher yield was characterized as NapA by electronic absorption and electron paramagnetic resonance spectroscopies and was identified by LC/MS/MS and MALDI-TOF/TOF MS as NapA from the napEDABC-type operon. The other 90kDa protein, which was unstable and produced in low yields, was posited as NapA from the napDAGHB-type operon. Two napA genes have been sequenced from the napEDABC-type and napDAGHB-type operons of S. gelidimarina. Native NAP from S. putrefaciens was resolved as one NapA monomer and one NapAB heterodimer. Two amino acid substitutions in NapA correlated with the isolation of NAP as a NapA monomer or a NapAB heterodimer. The resolution of native, redox-active NapA isoforms in Shewanella provides new insight into the respiratory versatility of this genus, which has implications in bioremediation and the assembly of microbial fuel cells.
%Z FOR Codes: 60503 60107 60114


%0 Journal Article
%A Fainerman-Melnikova, Marina
%A Clegg, Jack K
%A Pakchung, Amalie A H
%A Jensen, Paul
%A Codd, Rachel
%T Structural diversity of complexes between Cu(II) or Ni(II) and endocyclic oxygen- or nitrogen-containing ligands: synthesis, X-ray structure determinations and circular dichroism spectra
%B CrystEngComm
%D 2010
%C United Kingdom
%I Royal Society of Chemistry
%V 12
%N 
%P 4217-4225
%@ 1466-8033
%X 
%Z FOR Codes: 30402


%0 Journal Article
%~ PubMed
%A Simpson, Philippa J L
%A Richardson, David J
%A Codd, Rachel
%T The periplasmic nitrate reductase in Shewanella: the resolution, distribution and functional implications of two NAP isoforms, NapEDABC and NapDAGHB.
%B Microbiology (Reading, England)
%D 2010
%C United Kingdom
%I Society for General Microbiology
%V 156
%N 2
%P 302-12
%@ 1465-2080
%X In the bacterial periplasm, the reduction of nitrate to nitrite is catalysed by a periplasmic nitrate reductase (NAP) system, which is a species-dependent assembly of protein subunits encoded by the nap operon. The reduction of nitrate catalysed by NAP takes place in the 90 kDa NapA subunit, which contains a Mo-bis-molybdopterin guanine dinucleotide cofactor and one [4Fe-4S] iron-sulfur cluster. A review of the nap operons in the genomes of 19 strains of Shewanella shows that most genomes contain two nap operons. This is an unusual feature of this genus. The two NAP isoforms each comprise three isoform-specific subunits - NapA, a di-haem cytochrome NapB, and a maturation chaperone NapD - but have different membrane-intrinsic subunits, and have been named NAP-alpha (NapEDABC) and NAP-beta (NapDAGHB). Sixteen Shewanella genomes encode both NAP-alpha and NAP-beta. The genome of the vigorous denitrifier Shewanella denitrificans OS217 encodes only NAP-alpha and the genome of the respiratory nitrate ammonifier Shewanella oneidensis MR-1 encodes only NAP-beta. This raises the possibility that NAP-alpha and NAP-beta are associated with physiologically distinct processes in the environmentally adaptable genus Shewanella.
%Z FOR Codes: 60503 69999


%0 Journal Article
%A Liu, J
%A Clegg, J K
%A Codd, Rachel
%T 2,5-Dioxopyrrolidin-1-yl adamantane-1-carboxylate
%B Acta Crystallographica. Section E: Structure Reports Online
%D 2009
%C Denmark
%I Wiley-Blackwell Munksgaard
%V E65
%N 8
%P o1740-o1741
%@ 1600-5368
%X 
%Z FOR Codes: 30201


%0 Journal Article
%A Liu, J
%A Clegg, J K
%A Codd, Rachel
%T Methyl 3-[(1-adamantylcarbonyloxy)aminocarbonyl]propanoate
%B Acta Crystallographica. Section E: Structure Reports Online
%D 2009
%C Denmark
%I Wiley-Blackwell Munksgaard
%V E65
%N 8
%P o1742-o1743
%@ 1600-5368
%X 
%Z FOR Codes: 30201


%0 Journal Article
%~ PubMed
%A Codd, Rachel
%A Braich, Najwa
%A Liu, Joe
%A Soe, Cho Zin
%A Pakchung, Amalie A H
%T Zn(II)-dependent histone deacetylase inhibitors: Suberoylanilide hydroxamic acid and trichostatin A.
%B The international journal of biochemistry & cell biology
%D 2009
%C United Kingdom
%I Pergamon
%V 41
%N 4
%P 736-9
%@ 1357-2725
%X Suberoylanilide hydroxamic acid (SAHA, vorinostat, Zolinza) and trichostatin A (TSA) are inhibitors of the Zn(II)-dependent class I and class II histone deacetylases (HDACs), which are enzymes that operate in concert with histone acetyltransferases (HATs) to regulate the acetylation status of the epsilon-amino group of lysine residues of nucleosomal histones in chromatin. An increased level of histone acetylation resulting from the SAHA or TSA inhibition of Zn(II)-dependent HDACs relaxes the chromatin structure and upregulates transcription. The links made in the 1990s between the inhibition of HDAC activity and the suppression of tumor growth have brought the design of HDAC inhibitors (HDACi) to the forefront of oncology research. SAHA has anticancer activity against hematologic and solid tumors and has been approved by the FDA for the treatment of cutaneous T-cell lymphoma. The increased molecular-level understanding of class I and class IIa HDACs from X-ray crystallography highlights differences in the residues distal to the active site and in the cavity size, which has implications for HDACi substrate specificity and enzyme mechanism. Results from HDAC-focussed activity-based protein profiling experiments may lead to the design of molecules that are class-specific HDACi.
%Z FOR Codes: 110199


%0 Journal Article
%~ PubMed
%A Braich, Najwa
%A Codd, Rachel
%T Immobilised metal affinity chromatography for the capture of hydroxamate-containing siderophores and other Fe(iii)-binding metabolites directly from bacterial culture supernatants.
%B The Analyst
%D 2008
%C United Kingdom
%I Royal Society of Chemistry
%V 133
%N 7
%P 877-880
%@ 1364-5528
%X Nickel(ii)-based immobilized metal affinity chromatography (IMAC) has been used to capture from standard samples the hydroxamate-containing siderophores, acetohydroxamic acid (ahaH), suberodihydroxamic acid (shaH(2)) or desferrioxamine B (DFOB) in recoveries ranging between 35-90%. The capacity of a 1 mL Ni(ii)-charged IMAC column towards DFOB capture at the pH optima of 8.9 is approximately 3000 nmol. This method has been used for the direct capture of DFOB ( approximately 65% recovery) from the untreated supernatant of iron-deprived cultures of Streptomyces pilosus, the soil bacterium from which DFOB was first discovered. In addition to selecting for DFOB and a related siderophore, two other Fe(iii)-responsive species have been identified from RP-HPLC analysis of the IMAC-processed eluant from the S. pilosus supernatant. Since the characterisation of siderophores from natural systems is hampered by the low yields obtained from traditional purification methods, this IMAC-based affinity method offers significant potential for improving yields of this key class of bioligands and other small molecule metabolites with affinities to IMAC-compatible metal ions.
%Z FOR Codes: 110101 110502


%0 Journal Article
%~ PubMed
%A Pakchung, Amalie A H
%A Soe, Cho Z
%A Codd, Rachel
%T Studies of Iron-Uptake Mechanisms in Two Bacterial Species of the Shewanella Genus Adapted to Middle-Range (Shewanella putrefaciens) or Antarctic (Shewanella gelidimarina) Temperatures.
%B Chemistry & biodiversity
%D 2008
%C Germany
%I Wiley - VCH Verlag GmbH & Co. KGaA
%V 5
%N 10
%P 2113-23
%@ 1612-1880
%X Iron(III)-uptake mechanisms in bacteria indigenous to the Antarctic, which is the most Fe-deficient continent on Earth, have not been extensively studied. The cold-adapted, Antarctic bacterium, Shewanella gelidimarina, does not produce detectable levels of the siderophore, putrebactin, in the supernatant of Fe(III)-deprived cultures. This is distinct from the putrebactin-producing bacterium from the same genus, Shewanella putrefaciens, which is adapted to middle-range temperatures. The production of putrebactin by S. putrefaciens is optimal, when the pH value of the medium is 7.0. According to the strong positive response from whole cells in the Chrome Azurol S (CAS) agar diffusion assay, Shewanella gelidimarina appears to produce cell-associated siderophores. In the RP-HPLC trace of an Fe(III)-loaded extract from the cell-associated components of S. gelidimarina cultured in media with [Fe(III)] ca. 0 microM, a peak appears at [MeCN] ca. 77%, which decreases in intensity in a parallel experiment in which [Fe(III)] ca. 5 microM, and is barely detectable in Fe(III)-replete media ([Fe(III)] ca. 20 microM). The Fe(III)-dependence of this peak suggests that the attendant species, which is significantly more hydrophobic than putrebactin (RP-HPLC elution: [MeCN] ca. 14%), is associated with Fe(III)-management in S. gelidimarina. This study highlights the diversity in Fe(III)-uptake mechanisms in Shewanella species adapted to different environmental and thermal niches.
%Z FOR Codes: 110103


%0 Journal Article
%A Codd, Rachel
%T Traversing the coordination chemistry and chemical biology of hydroxamic acids
%B Coordination Chemistry Reviews
%D 2008
%C Netherlands
%I Elsevier BV
%V 252
%N 
%P 1387-1408
%@ 0010-8545
%X 
%Z FOR Codes: 110302


%0 Journal Article
%A Fainerman-Melnikova, Marina
%A Clegg, Jack K
%A Codd, Rachel
%T Aqua[bis(2-pyridylmethyl)amine][chelidonato(1.5-)]copper(II) chelidonate(0.5-) monohydrate
%B Acta Crystallographica. Section E: Structure Reports Online
%D 2006
%C Denmark
%I Wiley-Blackwell Munksgaard
%V 62
%N 
%P m3582-m3584
%@ 1600-5368
%X 
%Z FOR Codes: 110302


%0 Journal Article
%~ PubMed
%A Codd, Rachel
%A Lay, Peter A
%A Tsibakhashvili, Nelly Ya
%A Kalabegishvili, Tamaz L
%A Murusidze, Ivane G
%A Holman, Hoi-Ying N
%T Chromium(V) complexes generated in Arthrobacter oxydans by simulation analysis of EPR spectra.
%B Journal of inorganic biochemistry
%D 2006
%C United States
%I Elsevier Science Inc
%V 100
%N 11
%P 1827-33
%@ 0162-0134
%X Chromium(V) is an intermediate formed during the reduction of Cr(VI) to Cr(III) compounds by various bacteria. However, little is known about the nature, localization and reactivity of Cr(V) species in microbial systems. Electron paramagnetic resonance (EPR) spectroscopy was used to study the nature of Cr(V) complexes generated in basalt-inhabiting Gram-positive Arthrobacter oxydans bacteria after exposure to high concentrations of Cr(VI). Numerical simulations of the EPR spectroscopic data provide strong evidence for at least two different diolato-type oxoCr(V) complexes (I, g(iso)=1.9801; II, g(iso)=1.9796) involving bacterial cell wall macromolecules in the Cr(VI)-A. oxydans system. The relative concentrations of the two oxoCr(V)-diolato species differ when Cr(VI) is incubated with either untreated A. oxydans cells (I:II approximately 50:50) or lyophilized cells (I:II approximately 10:90). Based upon the magnitudes of the proton superhyperfine coupling constants ((1)H a(iso)) for species I and II, the EPR simulation model is unable to distinguish unambiguously whether the oxoCr(V)-diolato species are linear alkoxides or cyclic diols (carbohydrates). The oxygen-containing functional groups associated with teichoic acids are the most likely candidates for complexation with the Cr(V) ion.
%Z FOR Codes: 30201


%0 Journal Article
%A Pakchung, Amalie A. H.
%A Simpson, Philippa J. L.
%A Codd, Rachel
%T Life on Earth. Extremophiles Continue to Move the Goal Posts
%B Environmental Chemistry
%D 2006
%C Australia
%I CSIRO Publishing
%V 3
%N 2
%P 77-93
%@ 1448-2517
%X 
%Z FOR Codes: 110302