Candida proteases and their inhibition: prospects for antifungal therapy.
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.
Stewart
K
K
Department of Structural Biology, Abbott Laboratories, Abbott Park, IL 60064, USA. STEWARTK@RAND.PPRD.Abbott.Com
Abad-Zapatero
C
C
D000935:Antifungal Agents / Q000627:therapeutic use*; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002177:Candidiasis / Q000188:drug therapy* / Q000201:enzymology; D005656:Fungal Proteins; D017320:HIV Protease Inhibitors / Q000737:chemistry / Q000627:therapeutic use; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D010879:Piperazines / Q000737:chemistry / Q000627:therapeutic use*; D011480:Protease Inhibitors / Q000737:chemistry / Q000627:therapeutic use*; D013329:Structure-Activity Relationship
D000935:Antifungal Agents; D005656:Fungal Proteins; D017320:HIV Protease Inhibitors; D010879:Piperazines; D011480:Protease Inhibitors; C083088:A 70450; D016282:Aspartic Acid Endopeptidases; C079801:SAPP1 protein, Candida parapsilosis