High throughput screen for inhibitors of the folate biosynthetic pathway in bacteria
AssigneeMillennium Pharmaceuticals, Inc.
InventorChristopher K. Murphy
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Abstract
Methods for identifying compounds that are inhibitors of bacterial tetrahydrofolate biosynthesis are disclosed. Such compounds can be used as lead compounds in methods for preparing antibacterial agents for treating bacterial infections (e.g., in humans, animals, and plants). The disclosed methods allow for high throughput screening of libraries of test compounds.
Claims35
A method for determining whether a test compound is an inhibitor of bacterial tetrahydrofolate biosynthesis, the method comprising:
- (i) contacting a bacterial cell with a test compound, wherein the bacterial cell contains a promoter, the activity of which is increased in the presence of a compound that inhibits tetrahydrofolate biosynthesis;
- and
- (ii) measuring activity of the promoter, wherein an increase in activity, relative to the level of activity of the promoter in the absence of the test compound, indicates that the test compound is an inhibitor of bacterial tetrahydrofolate biosynthesis.
A method for determining whether a test compound is an inhibitor of bacterial tetrahydrofolate biosynthesis, the method comprising:
- (i) contacting a bacterial cell with a test compound, wherein the bacterial cell contains
- (a) a promoter, the activity of which is increased in the presence of a compound that inhibits tetrahydrofolate biosynthesis, operably linked to
- (b) a reporter gene;
- and
- (ii) measuring activity of the promoter, wherein an increase in activity, relative to the level of activity of the promoter in the absence of the test compound, indicates that the test compound is an inhibitor of bacterial tetrahydrofolate biosynthesis.
A method for determining whether a test compound is an antibacterial agent, the method comprising:
- (i) contacting a bacterial cell with a test compound, wherein the bacterial cell contains
- (a) a promoter, the activity of which is increased in the presence of a compound that inhibits tetrahydrofolate biosynthesis, operably linked to
- (b) a reporter gene;
- (ii) measuring activity of the promoter, wherein an increase in activity, relative to the level of activity of the promoter in the absence of the test compound, indicates that the test compound is an inhibitor of bacterial tetrahydrofolate biosynthesis;
- and
- (iii) determining whether the inhibitor of tetrahydrofolate biosynthesis inhibits the growth of a bacterium, wherein a compound that inhibits the growth of a bacterium is an antibacterial agent.
Dependencies are inferred from the claim text.