Isolated and purified 12R-lipoxygenase polypeptide and polynucleic acid encoding the same
OwnerAlan R. Brash, William E. Boeglin +1inventors
InventorsAlan R. Brash, William E. Boeglin, Richard B. Kim
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Abstract
Isolated and purified lipoxygenase proteins and nucleic acids are described. Particularly, a novel human 12R-lipoxygenase (12R-LO) protein and cDNA are described. Recombinant host cells, recombinant nucleic acids and recombinant proteins are also described, along with methods of producing each. Isolated and purified antibodies to 12R-LO, and methods of producing the same, are also described.
Claims61
An isolated and purified biologically active vertebrate lipoxygenase polypeptide capable of converting arachidonic acid to 12R-hydroxyeicosatetraenoic acid.
An isolated and purified nucleic acid segment comprising an isolated gene encoding a biologically active vertebrate lipoxygenase polypeptide capable of converting arachidonic acid to 12R-hydroxyeicosatetraenoic acid.
A method of screening candidate substances for their ability to modulate arachidonic acid metabolism, the method comprising the steps of:
- (a) establishing replicate test and control samples that comprise arachidonic acid and a vertebrate lipoxygenase polypeptide capable of converting arachidonic acid to 12R-hydroxyeicosatetraenoic acid;
- (b) administering a candidate substance to test sample but not the control sample;
- (c) measuring 12R-hydroxyeicosatetraenoic acid levels in the test and the control samples;
- and
- (d) determining that the candidate substance modulates arachidonic acid metabolism if the 12R-hydroxyeicosatetraenoic acid level measured for the test sample is greater or less than the 12R-hydroxyeicosatetraenoic acid level measured for the control sample.
A method of modulating vertebrate 12R-lipoxygenase polypeptide activity in a vertebrate, the method comprising the step of administering to the vertebrate an effective amount of a substance capable of modulating the 12R-lipoxygenase polypeptide activity in the vertebrate, whereby modulation of the 12R-lipoxygenase polypeptide activity is accomplished.
A method of treating a patient suffering from a disorder associated with 12R-LO activity in the patient, the method comprising the step of administering to the patient an effective amount of a substance capable of modulating the 12R-LO activity in the patient, whereby treatment of the disorder is accomplished.
A transgenic non-human animal having incorporated into its genome a nucleic acid segment comprising an isolated gene encoding a biologically active vertebrate lipoxygenase polypeptide capable of converting arachidonic acid to 12R-hydroxyeicosatetraenoic acid, the nucleic acid segment being present in said genome in a copy number effective to confer expression in the animal of the lipoxygenase polypeptide.
Dependencies are inferred from the claim text.