Publications
169 results found
Schroeder M, Hogwood J, Gray E, et al., 2011, Protamine neutralisation of low molecular weight heparins and their oligosaccharide components, ANALYTICAL AND BIOANALYTICAL CHEMISTRY, Vol: 399, Pages: 763-771, ISSN: 1618-2642
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- Citations: 44
Rudd TR, Gaudesi D, Skidmore MA, et al., 2011, Construction and use of a library of <i>bona fide</i> heparins employing <SUP>1</SUP>H NMR and multivariate analysis, ANALYST, Vol: 136, Pages: 1380-1389, ISSN: 0003-2654
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- Citations: 21
Chang SC, Mulloy B, Magee AI, 2011, Two distinct sites in sonic hedgehog combine for heparan sulfate interactions and cell signaling functions, Journal of Biological Chemistry
Hedgehog (Hh) proteins are morphogens that mediate many developmental processes. Hh signaling is significant for many aspects of embryonic development, whereas dysregulation of this pathway is associated with several types of cancer. Hh proteins require heparan sulfate proteoglycans (HSPGs) for their normal distribution and signaling activity. Here we have used molecular modelling to examine the heparin-binding domain of Shh. In biochemical and cell biological assays the importance of specific residues of the putative heparin-binding domain for signaling were assessed. It was determined that key residues in hShh involved in heparin and HSPG syndecan-4 binding and biological activity included the well known cationic Cardin-Weintraub motif (lysine 32-lysine38), but also a previously unidentified major role for lysine 178. The activity of Shh mutated in these residues was tested by quantitation of alkaline phosphatase activity in C3H10T1/2 cells differentiating into osteoblasts and hShh-inducible gene expression in PANC1 human pancreatic ductal adenocarcinoma (PDAC) cells. Mutated hShhs such as K37/38S, K178S and particularly K37/38/178S that could not interact with heparin efficiently had reduced signaling activity compared to wild type hShh or a control mutation (K74S). In addition, the mutant hShh proteins supported reduced proliferation and invasion of PANC1 cells compared with control hShh proteins, following endogenous hShh depletion by RNAi knockdown. The data correlated with reduced Shh multimerization where the K37/38 and/or K178 mutations were examined. These studies provide a new insight into the functional roles of hShh interactions with HSPGs, which may allow targeting this aspect of hShh biology in, for example, PDAC.
Rudd TR, Gaudesi D, Lima MA, et al., 2011, High-sensitivity visualisation of contaminants in heparin samples by spectral filtering of <SUP>1</SUP>H NMR spectra, ANALYST, Vol: 136, Pages: 1390-1398, ISSN: 0003-2654
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- Citations: 21
Troeberg L, Mulloy B, Lee M-H, et al., 2010, Calcium pentosan polysulfate increases affinity between aggrecanases (ADAMTS-4 and-5) and TIMP-3 by a conformational change, Spring Meeting of the British-Society-for-Matrix-Biology, Publisher: WILEY-BLACKWELL, Pages: A40-A40, ISSN: 0959-9673
Bednarek E, Sitkowski J, Bocian W, et al., 2010, An assessment of polydispersed species in unfractionated and low molecular weight heparins by diffusion ordered nuclear magnetic resonance spectroscopy method, JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, Vol: 53, Pages: 302-308, ISSN: 0731-7085
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- Citations: 21
Mulloy B, Corfield AP, 2010, Structural Glycobiology and Human Health, BIOCHEMICAL SOCIETY TRANSACTIONS, Vol: 38, Pages: 1329-1332, ISSN: 0300-5127
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- Citations: 1
Boraston A, Mulloy B, 2010, Structural glycobiology: biosynthesis, recognition events, and new methods, CURRENT OPINION IN STRUCTURAL BIOLOGY, Vol: 20, Pages: 533-535, ISSN: 0959-440X
Khan S, Miller A, Gor J, et al., 2010, Oligomeric solution structures of factor H in the presence of heparin fragments, 23rd International National Complement Workshop, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 2264-2264, ISSN: 0161-5890
Rider CC, Mulloy B, 2010, Bone morphogenetic protein and growth differentiation factor cytokine families and their protein antagonists, BIOCHEMICAL JOURNAL, Vol: 429, Pages: 1-12, ISSN: 0264-6021
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- Citations: 167
Mulloy B, Hogwood J, Gray E, 2010, Assays and reference materials for current and future applications of heparins, BIOLOGICALS, Vol: 38, Pages: 459-466, ISSN: 1045-1056
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- Citations: 19
Severin IC, Gaudry J-P, Johnson Z, et al., 2010, Characterization of the Chemokine CXCL11-Heparin Interaction Suggests Two Different Affinities for Glycosaminoglycans, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 285, Pages: 17713-17724
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- Citations: 48
Khan S, Gor J, Mulloy B, et al., 2010, Semi-Rigid Solution Structures of Heparin by Constrained X-ray Scattering Modelling: New Insight into Heparin-Protein Complexes, JOURNAL OF MOLECULAR BIOLOGY, Vol: 395, Pages: 504-521, ISSN: 0022-2836
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- Citations: 82
Marson A, Robinson DE, Brookes PN, et al., 2009, Development of a microtiter plate-based glycosaminoglycan array for the investigation of glycosaminoglycan-protein interactions, GLYCOBIOLOGY, Vol: 19, Pages: 1537-1546, ISSN: 0959-6658
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- Citations: 36
Zhang Z, Li B, Suwan J, et al., 2009, Analysis of Pharmaceutical Heparins and Potential Contaminants Using <SUP>1</SUP>H-NMR and PAGE, JOURNAL OF PHARMACEUTICAL SCIENCES, Vol: 98, Pages: 4017-4026, ISSN: 0022-3549
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- Citations: 64
Mulloy B, Khan S, Perkins S, et al., 2009, Heparin-Protein Interactions: A Three-Dimensional Approach, Annual Meeting of the Society-for-Glycobiology, Publisher: OXFORD UNIV PRESS INC, Pages: 1296-1296, ISSN: 0959-6658
Zhang Z, Li B, Suwan J, et al., 2009, CARB 86-Analysis of pharmaceutical heparins and potential contaminants using 1H-NMR and PAGE, Publisher: AMER CHEMICAL SOC, ISSN: 0065-7727
Gray E, Mulloy B, 2009, Biosimilar low molecular weight heparin products, JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Vol: 7, Pages: 1218-1221, ISSN: 1538-7933
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- Citations: 20
Veverka V, Henry AJ, Slocombe PM, et al., 2009, Characterization of the Structural Features and Interactions of Sclerostin <i>MOLECULAR INSIGHT INTO A KEY REGULATOR OF Wnt-MEDIATED BONE FORMATION</i>, JOURNAL OF BIOLOGICAL CHEMISTRY, Vol: 284, Pages: 10890-10900, ISSN: 0021-9258
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- Citations: 185
Troeberg L, Mulloy B, Nagase H, 2009, What is the minimal length of calcium pentosan polysulfate that is able to block aggrecan breakdown in cartilage?, Annual General Meeting of the British-Society-for-Matrix-Biology, Publisher: WILEY-BLACKWELL PUBLISHING, INC, Pages: A133-A133, ISSN: 0959-9673
Fermas S, Gonnet F, Sutton A, et al., 2008, Sulfated oligosaccharides (heparin and fucoidan) binding and dimerization of stromal cell-derived factor-1 (SDF-1/CXCL 12) are coupled as evidenced by affinity CE-MS analysis, GLYCOBIOLOGY, Vol: 18, Pages: 1054-1064, ISSN: 0959-6658
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- Citations: 48
McEwen I, Mulloy B, Hellwig E, et al., 2008, Determination of Oversulphated Chondroitin Sulphate and Dermatan Sulphate in unfractionated heparin by (1)H-NMR - Collaborative study for quantification and analytical determination of LoD., Pharmeuropa Bio, Vol: 2008, Pages: 31-39, ISSN: 1684-7075
Oversulphated Chondroitin Sulphate (OSCS) and Dermatan Sulphate (DS) in unfractionated heparins can be identified by nuclear magnetic resonance spectrometry (NMR). The limit of detection (LoD) of OSCS is 0.1% relative to the heparin content. This LoD is obtained at a signal-to-noise ratio (S/N) of 2000:1 of the heparin methyl signal. Quantification is best obtained by comparing peak heights of the OSCS and heparin methyl signals. Reproducibility of less than 10% relative standard deviation (RSD) has been obtained. The accuracy of quantification was good.
Khan S, Gor J, Mulloy B, et al., 2008, Solution structure of heparin and its complexes with the factor H SCR-6/8 domains and factor H: Implications for disease, 22nd International Complement Workshop, Publisher: PERGAMON-ELSEVIER SCIENCE LTD, Pages: 4126-4126, ISSN: 0161-5890
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- Citations: 3
Jose Uria M, Zhang Q, Li Y, et al., 2008, A generic mechanism in <i>Neisseria meningitidis</i> for enhanced resistance against bactericidal antibodies, JOURNAL OF EXPERIMENTAL MEDICINE, Vol: 205, Pages: 1423-1434, ISSN: 0022-1007
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- Citations: 63
Gray E, Mulloy B, Barrowcliffel TW, 2008, Heparin and low-molecular-weight heparin, THROMBOSIS AND HAEMOSTASIS, Vol: 99, Pages: 807-818, ISSN: 0340-6245
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- Citations: 216
Mulloy B, Forster MJ, 2008, Application of drug discovery software to the identification of heparin-binding sites on protein surfaces: a computational survey of the 4-helix cytokines, MOLECULAR SIMULATION, Vol: 34, Pages: 481-489, ISSN: 0892-7022
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- Citations: 24
Mulloy B, Heath A, Behr-Gross M-E, 2007, Establishment of replacement batches for heparin low-molecular-mass for calibration CRS, and the International Standard Low Molecular Weight Heparin for Calibration., Pharmeuropa Bio, Vol: 2007, Pages: 29-48, ISSN: 1684-7075
An international collaborative study involving fourteen laboratories has taken place, organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM) with National Institute for Biological Standards & Control (NIBSC) (in its capacity as a World Health Organisation (WHO) Laboratory for Biological Standardisation) to provide supporting data for the establishment of replacement batches of Heparin Low-Molecular-Mass (LMM) for Calibration Chemical Reference Substance (CRS), and of the International Reference Reagent (IRR) Low Molecular Weight Heparin for Molecular Weight Calibration. A batch of low-molecular-mass heparin was donated to the organisers and candidate preparations of freeze-dried heparin were produced at NIBSC and EDQM. The establishment study was organised in two phases: a prequalification (phase 1, performed in 3 laboratories in 2005) followed by an international collaborative study (phase 2). In phase 2, started in March 2006, molecular mass parameters were determined for seven different LMM heparin samples using the current CRS batch and two batches of candidate replacement material with a defined number average relative molecular mass (Mn) of 3,700, determined in phase 1. The values calculated using the candidates as standard were systematically different from values calculated using the current batch with its assigned number-average molecular mass (Mna) of 3,700. Using raw data supplied by participants, molecular mass parameters were recalculated using the candidates as standard with values for Mna of 3,800 and 3,900. Values for these parameters agreed more closely with those calculated using the current batch supporting the fact that the candidates, though similar to batch 1 in view of the production processes used, differ slightly in terms of molecular mass distribution. Therefore establishment of the candidates was recommended with an assigned Mna value of 3,800 that is both consistent with phase 1 results and guarante
Gutierrez T, Mulloy B, Black K, et al., 2007, Glycoprotein emulsifiers from two marine <i>Halomonas</i> species:: chemical and physical characterization, JOURNAL OF APPLIED MICROBIOLOGY, Vol: 103, Pages: 1716-1727, ISSN: 1364-5072
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- Citations: 62
Mummery RS, Mulloy B, Rider CC, 2007, The binding of human betacellulin to heparin, heparan sulfate and related polysaccharides, GLYCOBIOLOGY, Vol: 17, Pages: 1094-1103, ISSN: 0959-6658
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- Citations: 9
Gutierrez T, Mulloy B, Bavington C, et al., 2007, Partial purification and chemical characterization of a glycoprotein (putative hydrocolloid) emulsifier produced by a marine bacterium <i>Antarctobacter</i>, APPLIED MICROBIOLOGY AND BIOTECHNOLOGY, Vol: 76, Pages: 1017-1026, ISSN: 0175-7598
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- Citations: 31
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