Inhibition of Candida albicans secreted aspartic protease by a novel series of peptidomimetics, also active on the HIV-1 protease.
Nineteen reduced amide, monohydroxy- or dihydroxyethylene-based transition-state peptidomimetics, known to be good inhibitors of the aspartic protease of HIV-1, were tested against a secreted aspartic protease (Sap2), purified from the culture medium of a virulent strain of Candida albicans. Ten of these compounds exhibited IC(50)s against Sap2 lower than 15 microM; the best inhibitor, Kyn-Val-Phe-Psi[OH-OH]-Phe-Val-Kyn, when added to the C. albicans culture, repressed the hydrolysis of bovine serum albumin (BSA), contained in the culture medium, and inhibited the growth of the fungus.
Skrbec
Damiano
D
Department of Biochemistry, Biophysics and Macromolecular Chemistry, University of Trieste, Via L. Giorgieri,1, I-34127, Trieste, Italy.
Romeo
Domenico
D
D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002176:Candida albicans / Q000201:enzymology*; D004591:Electrophoresis, Polyacrylamide Gel; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005656:Fungal Proteins; D017320:HIV Protease Inhibitors / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D004791:Enzyme Inhibitors; D005656:Fungal Proteins; D017320:HIV Protease Inhibitors; D010455:Peptides; D016282:Aspartic Acid Endopeptidases; C090753:SAP2 protein, Candida