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Candida proteases and their inhibition: prospects for antifungal therapy
1Department of Structural Biology, Abbott Laboratories, Abbott Park, IL 60064, USA. STEWARTK@RAND.PPRD.Abbott.Com
Current Medicinal Chemistry
|May 29, 2001
Abstract:
The rationale for inhibition of the secreted acid proteases (SAP) of Candida fungal species as a novel antifungal strategy is outlined. Enzyme structure-activity relationship data regarding the inhibitor A-70450 are described along with results from in vivo antifungal assays. Developments from protein X-ray crystallographic studies, SAP knock-out genetic studies, and the importance of these new results for drug discovery are reviewed. Finally, inhibition of the Candida SAP enzymes with HIV protease inhibitors and a proposed role in candidiasis of AIDS patients is discussed.