ASSAYS FOR MODULATORS OF ASPARAGINYL HYDROXYLASE

摘要

A method of identifying an agent which modulates hydroxylation of hypoxia inducible factor (HIF), comprises contacting a HIF asparagine hydroxylase and a test substance in the presence of a substrate of the hydroxylase under conditions in which asparagine in the substrate is hydroxylated in the absence of the test substance; and determining hydroxylation of the substrate. Preferably the substrate is a HIF polypeptide comprising HIF-lalpha, a fragment thereof comprising Asn 803 of HIF-lalpha or a peptide analogue of HIF-lalpha or fragment thereof comprising an asparagine equivalent to Asn 803 of HIF-lalpha and wherein hydroxylation of Asn 803 or of a said equivalent asparagine is determined.