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US 8,557,746 B2Granted
High throughput screens for small-molecule inhibitors of the nuclear receptor-like pathway regulating multidrug resistance in fungi
AssigneesThe General Hospital Corporation, President and Fellows of Harvard College
InventorsAnders M. Naar, Gerhard Wagner, Joy Nishikawa, Haribabu Arthanari
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Abstract
The present invention relates to the identification of molecular mechanisms associated with multidrug resistance (MDR) in fungal infections. More specifically, fungi harbor a nuclear receptor-like pathway controlling MDR, which represents a novel therapeutic target for the treatment of MDR in pathogenic fungi such as C. glabrata.
Claims4
A method for the high throughput screening for agents that inhibit the multidrug resistance pathway in fungi comprising:
- providing a solution of fluorescein-labeled Pdr1p activation domain, a Gal11p
- KIX domain and a test agent;
- and
- comparing the fluorescence polarization of the solution of fluorescein-labeled Pdr1p activation domain, the Gal11p KIX domain and the test agent, with the fluorescence polarization of a solution of fluorescein-labeled Pdr1p activation domain and a Gal11p KIX domain;
- wherein the fluorescein-labeled Pdr1p activation domain consists of fluorescein and 30 amino acids of the CgPdr1p activation domain, having the amino acid sequence
- LGTLDEFVNKGDLNELYNSLWGDLFSDVYL.
- (SEQ ID NO:
- 14)
5 more elements
Dependencies are inferred from the claim text.