Assays and reagents for identifying anti-fungal agents, and uses related thereto
AssigneeGPC Biotech AG
InventorsVivian Berlin, Veronique Damagnez, Susan E. Smith
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Abstract
The present invention relates to rapid, reliable and effective assays for screening and identifying pharmaceutically effective compounds that specifically inhibit the biological activity of fungal GTPase proteins, particularly GTPases involved in cell wall integrity, hyphael formation, and/or other cellular functions critical to pathogenesis. Another aspect of the present invention relates to novel Candida genes and gene products
Claims36
A purified and/or recombinant polypeptide comprising a GTPase sequence encodable by a nucleic acid which hybridizes under stringent conditions to SEQ ID No. 1 or SEQ ID No. 5, the GTPase sequence (i) directing the binding of said polypeptide to a glucan synthase subunit, (ii) directing the binding of said polypeptide to PKC, (iii) serving as a substrate for prenylation by a GGPTase, or (iv) having a GTP hydrolytic activity, or a combination thereof.
A purified and/or recombinant polypeptide comprising a GGTase sequence encodable by a nucleic acid which hybridizes under stringent conditions to SEQ ID No. 3 or 7, the GGTase sequence (i) directing the binding of said polypeptide to other GGPTase subunit(s), or (ii) directing the binding of said polypeptide to a Rho1-like GTPase, or a combination thereof.
The polypeptide of claim 8, wherein said Candida spp is selected from the group consisting of Candida albicans, Candida stellatoidea, Candida tropicalis, Candida parapsilosis, Candida krusei, Candida pseudotropicalis, Candida quillermondii and Candida rugosa.
An isolated nucleic acid which specifically hybridizes to the nucleic acid sequence of SEQ ID No. 1 (sense or antisense) and selectively detects a CaRho1 gene encoding a protein having GTP hydrolytic activity.
An isolated nucleic acid which specifically hybridizes to the nucleic acid sequence of SEQ ID No. 5 (sense or antisense) and selectively detects a CaCdc42 gene encoding a protein having GTP hydrolytic activity.
An isolated nucleic acid which specifically hybridizes to the nucleic acid sequence of SEQ ID No. 3 or 7 (sense or antisense) and selectively detects a CaRAM2 or CaCal1 gene encoding a GGPTase or FPTase subunit.
A method for detecting the presence of Candida cells comprising detecting, in a sample, the presence of one or more of a (i) a nucleic acid encoding a Candida protein selected from the group consisting of CaRho1, CaCdc42 and CaRAM2, and (ii) a Candida protein selected from the group consisting of CaRho1, CaCdc42 and CaRAM2.
Dependencies are inferred from the claim text.