摘要:
The present invention relates to assays for monitoring activity of OGFOD1 activity, in particular, to assays for identifying modulators of OGFOD1 activity. The invention also relates to assays to monitor the prolyl hydroxylase activity of OGFOD1 on its substrate, the human ribosomal protein RPS23. The invention also enables the introduction of 3-hydroxyprolyl residues into peptides and proteins.
摘要:
A method of identifying, screening, characterising or designing a chemical entity, which mimics or binds to FIH, is described. The method comprises comparing a structural model of FIH with a structural model for said chemical entity, wherein said structural model of FIH is derived from structural factors or structural coordinates determined by subjecting to X-ray diffraction measurements a crystal comprising FIH. Such chemical entities may be used in the treatment of a condition associated with increased or decreased HIF levels or activity.
摘要:
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.
摘要:
Nucleic acid constructs comprising hypoxia response elements in operable linkage with a coding sequence of a gene of interest, and methods for expressing a nucleic acid sequence using the constructs, are disclosed. In particular, such nucleic acid constructs comprise genes encoding prodrug activation systems or cytokines.
摘要:
Nucleic acid constructs comprising hypoxia response elements in operable linkage with a coding sequence of a gene of interest are disclosed. In particular, such nucleic acid constructs comprise genes encoding pro-drug activation systems or cytokines.
摘要:
The present invention relates to assays for monitoring activity of OGFOD1 activity, in particular, to assays for identifying modulators of OGFOD1 activity. The invention also relates to assays to monitor the prolyl hydroxylase activity of OGFOD1 on its substrate, the human ribosomal protein RPS23. The invention also enables the introduction of 3-hydroxyprolyl residues into peptides and proteins.
摘要:
The present invention relates to assays for monitoring activity of Mina53 and NO66 activities, in particular, to assays for identifying modulators of Mina53 and NO66 activities. The invention also relates to assays to monitor the histidinyl hydroxylase activity of Mina53 and NO66 on their substrates, the human ribosomal protein Rpl27a and Rpl8 respectively. The invention also enables the introduction of S-3-hydroxyhistidinyl residues into peptides and proteins.
摘要:
A novel class of hydroxylases is described having the amino acid sequence of SEQ ID NO: 2, 4, 6 and 8, and variants and fragments thereof having HIF hydroxylation activity. The polypeptides of the invention have in particular prolyl hydroxylase activity. An assay method monitors the interaction of the HIF hydroxylase with a substrate. Modulators of HIF hydroxylase are provided for use in the treatment of a condition associated with increased or decreased HIF levels or activity or for the treatment of a condition where it is desirable to modulate HIF levels or activity.
摘要翻译:描述了一类新型的羟化酶,其具有SEQ ID NO:2,4,6和8的氨基酸序列,其变体和片段具有HIF羟基化活性。 本发明的多肽特别是脯氨酰羟化酶活性。 测定方法监测HIF羟化酶与底物的相互作用。 提供HIF羟化酶的调节剂用于治疗与增加或降低的HIF水平或活性有关的病症,或用于治疗期望调节HIF水平或活性的病症。
摘要:
The invention relates to the finding that the VHL tumour suppressor protein regulates hypoxia inducible factor α subunits, by targeting HIF α for destruction in normoxic, but not hypoxic cells. The invention provides assays for modulators of this interaction, and peptides based upon HIF α subunit sequences which may modulate this interaction.
摘要:
The invention relates to the finding that the VHL tumour suppressor protein regulates hypoxia inducible factor α subunits, by targeting HIF α for destruction in normoxic, but not hypoxic cells. The invention provides assays for modulators of this interaction, and peptides based upon HIF α subunit sequences which may modulate this interaction.