Method for discovering substances for inhibiting enzymes
AssigneePharmacia & Upjohn Company
InventorsTimothy Geary, Margaret Favreau
Life of this patent
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Abstract
This invention describes novel methods for the identification of compounds useful as inhibitors of enzymes. The methods involve obtaining a target gene-complemented microorganism which is dependent on the expression of the target gene for survival in test conditions. By measuring the viability of the complemented microorganism after exposure to a compound, compounds that inhibit growth in test conditions are identified. These compounds that inhibit growth are further tested in conditions where the expression of the target gene is not required for growth in order to identify compounds that specifically inhibit the target gene but do not effect the viability of the host.
Claims39
A method for identifying a compound having antiparasitic activity comprising:
- a) exposing to the compound a parasite target gene-complemented microorganism growing in a selection conditions that inhibits the viability of non-complemented microorganisms;
- b) comparing the viability of the microorganism in the selection conditions after exposure to the compound to the viability of the microorganism in the selection conditions lacking the compound to identify a compound that decreases viability of the microorganism, thereby identifying a compound having antiparasitic activity.
A method for identifying a compound useful as an antiparasitic drug comprising:
- a) determining whether the compound decreases viability of a target gene-complemented microorganism by comparing the viability of a target gene-complemented microorganism growing in a selection medium after exposure to a compound to the viability of the target gene-complemented microorganism growing in the selection medium in the absence of the compound;
- b) comparing viability of the target gene-complemented microorganism after exposure to the compound in the absence of the selection conditions to viability of the microoganism in the absence of both the selection medium and the compound, thereby identifying a compound useful as an antiparasitic drug.
A method of screening for a compound or identifying a compound that inhibits an essential parasite gene product required for parasite viability, said method comprising:
- (a) rendering a microorganism incapable of growing under test conditions;
- (b) producing a target gene-complemented microorganism by complementing the microorganism of step (a) with parasite gene encoding an parasite gene product that enables the microbial strain to grow in test conditions;
- (c) exposing the target gene-complemented microorganism under test conditions to a compound to be tested for parasite gene product inhibitory properties and comparing the viability of the target gene-complemented microorganism exposed to the compound to the viability of the target gene-complemented microorganism in the absence of the compound.
- (d) determining whether the compound inhibits growth of the target gene-complemented microorganism, thereby identifying a compound that inhibits an essential parasite gene product.
A polypeptide sequence comprising SEQ ID NO:
- 6.
Dependencies are inferred from the claim text.