Abstract: A target asparagine residue of HIF 1 alpha and 2 alpha is hydroxylated at high oxygen tension to render HIF as a weak transcription factor. An asparagine hydroxylase hydroxylation motif and binding motif is proposed. A method of screening for agonists or antagonists of an asparagine hydroxylase is also proposed and involves mixing peptides or proteins having the hydroxylation and or the binding motif with asparagine hydroxylase and a candidate agonist or antagonist. The extent of inhibition or enhancement of binding; level of asparagine hydroxylation or transactivation may be measured depending on the nature of the protein or peptide. Additionally altered proteins resistant to hydroxylation are described as are nucleic acids encoding such proteins.

Abstract: The invention concerns novel compounds of the formula I ##STR1## wherein: A is selected from CH and N;B is selected from oxygen, sulfur, CH.sub.2 and the group N-Z wherein Z is selected from the group consisting of hydrogen, alkyl, alkenyl, alkynyl, cycloalkyl, benzyl and substituted benzyl;X, which may be the same or different, and X.sup.1, which be the same or different, are selected from halogen, nitro, cyano, alkyl, substituted alkyl, hydroxy, alkoxy, substituted alkoxy, alkenyl, alkenyloxy, alkynyl, alkynyloxy, acyloxy, alkoxycarbonyl, alkylthio, alkylsulfinyl, alkylsulfonyl, sulfamoyl, substituted sulfamoyl, alkanoyloxy, benzyloxy, substituted benzyloxy, amino, substituted amino, and the groups formyl and alkanoyl and the oxime, imine and Schiff base derivatives thereof;R.sup.1 is selected from hydrogen, alkyl, alkenyl, alkynyl, substituted alkyl, alkylsulfonyl, arylsulfonyl, acyl and an inorganic or organic cation;R.sup.