Dana-farber-cancer Institute Inc.

Mircea Ivan

William G Kaelin

Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. The ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is 'turned on' only under such conditions.

Pharmaceuticals and methods for treating hypoxia and screening methods therefor

Method of identifying a compound for treating a hypoxic or ischemic related disorder

The present invention provides methods of identifying compounds that decrease proline hydroxylation of the alpha subunit of hypoxia inducible factor (HIF&#x3b1;).

HIF&#x3b1; hydroxylation assay

HIF&#x3b1;prolyl hydroxylation assay

The present invention provides hypoxia inducible factor alpha muteins, DNA sequences encoding these hypoxia inducible factor alpha muteins, recombinant DNA molecules containing those DNA sequences operatively linked to expression control sequences and capable of inducing expression of an hypoxia inducible factor alpha muteins, hosts transformed with those recombinant DNA molecules, pharmaceutical compositions containing hypoxia inducible factor alpha muteins and methods of using those compositions to treat hypoxia and ischemic related tissue damage.

Muteins of hypoxia inducible factor alpha and methods of use thereof

Light-generating fusion proteins having a ligand binding site and a light-generating polypeptide moiety and their use as diagnostics, in drug screening and discovery, and as therapeutics, are disclosed. The light-generating fusion protein has a feature where the bioluminescence of the polypeptide moiety changes upon binding of a ligand at the ligand binding site. Tie ligand may be, for example, an enzyme present in an environment only under certain conditions, e.g., ubiquitin ligase in a hypoxic state, such that the light-generating fusion protein is 'turned on' only under such conditions.

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Cambridge, MA, United States of America

Mircea Ivan