Title:
ASSAYS FOR IDENTIFYING MODULATORS OF THE HYDROXYLATION OF ANKYRIN REPEAT PROTEINS BY 2-OXOGLUTARATE DEPENDENT OXIGENASE AND METHODS OF USING THE SAME
Document Type and Number:
WIPO Patent Application WO2005093411
Kind Code:
A3
Abstract:
A method of identifying an agent which modulates 2-oxoglutarate dependent oxygenase activity, the method comprising contacting a 2-oxoglutarate dependent oxygenase and a test agent in the presence of a substrate comprising one or more ankyrin repeat, or fragment thereof, in conditions under which the substrate is hydroxylated in the absence of the test agent; and determining hydroxylation of the substrate.
Inventors:
SCHOFIELD CHRISTOPHER JOSEPH (GB)
HEWITSON KIRSTY SARAH (GB)
MCDONOUGH MICHAEL ARNOLD (GB)
RATCLIFFE PETER JOHN (GB)
MASSON NORMA (GB)
COCKMAN MATTHEW EDWARD (GB)
HEWITSON KIRSTY SARAH (GB)
MCDONOUGH MICHAEL ARNOLD (GB)
RATCLIFFE PETER JOHN (GB)
MASSON NORMA (GB)
COCKMAN MATTHEW EDWARD (GB)
Application Number:
PCT/GB2005/001150
Publication Date:
February 02, 2006
Filing Date:
March 24, 2005
Export Citation:
Assignee:
ISIS INNOVATION (GB)
SCHOFIELD CHRISTOPHER JOSEPH (GB)
HEWITSON KIRSTY SARAH (GB)
MCDONOUGH MICHAEL ARNOLD (GB)
RATCLIFFE PETER JOHN (GB)
MASSON NORMA (GB)
COCKMAN MATTHEW EDWARD (GB)
SCHOFIELD CHRISTOPHER JOSEPH (GB)
HEWITSON KIRSTY SARAH (GB)
MCDONOUGH MICHAEL ARNOLD (GB)
RATCLIFFE PETER JOHN (GB)
MASSON NORMA (GB)
COCKMAN MATTHEW EDWARD (GB)
International Classes:
C12Q1/26; G01N33/50; (IPC1-7): C12N9/02; C12Q1/26
Domestic Patent References:
| WO2003100438A1 | 2003-12-04 | |||
| WO2002074981A2 | 2002-09-26 | |||
| WO2003100087A2 | 2003-12-04 |
Other References:
MOLE D.R. ET AL.: "2-oxoglutarate analogue inhibitors of HIF prolyl hydroxylase.", BIOORG. MED. CHEM. LETT., vol. 13, 18 September 2003 (2003-09-18), pages 2677 - 2680, XP002353945
LEE C. ET AL.: "Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau.", J. BIOL. CHEM., vol. 278, no. 9, 28 February 2003 (2003-02-28), pages 7558 - 7563, XP002353946
DANN C.E. ET AL.: "Structure of factor-inhibiting hypoxia-inducible factor 1 : an asparaginyl hydroxylase involved in the hypoxic response pathway.", PROC. NATL. ACAD. SCI. USA, vol. 99, no. 24, 26 November 2002 (2002-11-26), pages 15351 - 15356, XP002353947
ELKINS J.M. ET AL.: "Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1alpha.", J. BIOL. CHEM., vol. 278, no. 3, 17 January 2003 (2003-01-17), pages 1802 - 1806, XP002277421
HEWITSON K.S. ET AL.: "The role of iron and 2-oxoglutarate oxygenases in signalling.", BIOCHEM. SOC. TRANS., vol. 31, no. pt3, June 2003 (2003-06-01), pages 510 - 515, XP002353948
CIECHANOVER A. ET AL.: "Mechanisms of ubiquitin-mediated, limited processing of the NF-kappaB1 precursor protein p105.", BIOCHIMIE, vol. 83, 2001, pages 341 - 349, XP002353949
SEDGWICK S.G. ET AL.: "The ankyrin repeat: a diversity of interactions on a common structural framework.", TRENDS BIOCHEM. SCI., vol. 24, September 1999 (1999-09-01), pages 311 - 316, XP004174251
LEE C. ET AL.: "Structure of human FIH-1 reveals a unique active site pocket and interaction sites for HIF-1 and von Hippel-Lindau.", J. BIOL. CHEM., vol. 278, no. 9, 28 February 2003 (2003-02-28), pages 7558 - 7563, XP002353946
DANN C.E. ET AL.: "Structure of factor-inhibiting hypoxia-inducible factor 1 : an asparaginyl hydroxylase involved in the hypoxic response pathway.", PROC. NATL. ACAD. SCI. USA, vol. 99, no. 24, 26 November 2002 (2002-11-26), pages 15351 - 15356, XP002353947
ELKINS J.M. ET AL.: "Structure of factor-inhibiting hypoxia-inducible factor (HIF) reveals mechanism of oxidative modification of HIF-1alpha.", J. BIOL. CHEM., vol. 278, no. 3, 17 January 2003 (2003-01-17), pages 1802 - 1806, XP002277421
HEWITSON K.S. ET AL.: "The role of iron and 2-oxoglutarate oxygenases in signalling.", BIOCHEM. SOC. TRANS., vol. 31, no. pt3, June 2003 (2003-06-01), pages 510 - 515, XP002353948
CIECHANOVER A. ET AL.: "Mechanisms of ubiquitin-mediated, limited processing of the NF-kappaB1 precursor protein p105.", BIOCHIMIE, vol. 83, 2001, pages 341 - 349, XP002353949
SEDGWICK S.G. ET AL.: "The ankyrin repeat: a diversity of interactions on a common structural framework.", TRENDS BIOCHEM. SCI., vol. 24, September 1999 (1999-09-01), pages 311 - 316, XP004174251
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