Secreted aspartic proteases of Candida albicans, Candida tropicalis, Candida parapsilosis and Candida lusitaniae. Inhibition with peptidomimetic inhibitors
| Autor: | Tomáš Ruml, Milan Souček, Jan Weber, Olga Hrušková-Heidingsfeldová, Iva Pichová, L. Pavlíčková, Elena Dolejší, Jiří Dostál |
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| Rok vydání: | 2001 |
| Předmět: |
Proteases
medicine.medical_treatment Molecular Sequence Data In Vitro Techniques Candida parapsilosis Biochemistry Microbiology Substrate Specificity Candida tropicalis Candida albicans Pepstatins medicine Aspartic Acid Endopeptidases Humans Protease Inhibitors Amino Acid Sequence Candida Protease biology Sequence Homology Amino Acid Candida lusitaniae biology.organism_classification Corpus albicans Kinetics Saquinavir medicine.drug |
| Zdroj: | European journal of biochemistry. 268(9) |
| ISSN: | 0014-2956 |
| Popis: | The frequency of Candida infections has increased in recent years and it has been accompanied by a significant rise in morbidity and mortality. The secretion of aspartic proteases by Candida spp. was demonstrated to be one of the virulence determinants. Candida albicans is classified as the major human pathogen in the genus Candida. However, other species of this genus have been found to cause an increasing number of candidiases. We isolated secreted aspartic proteases (Saps) of C. albicans (Sap2p), C. tropicalis (Sapt1p), C. parapsilosis (Sapp1p), and C. lusitaniae (Saplp) from culture media. All the isolated proteases were N-terminally sequenced. Their specific proteolytic activities and sensitivity to series of peptidomimetic inhibitors modified in the type of scissile bond replacement as well as in the N- and C-termini were analyzed. The most divergent substrate specificity was observed for the Sap of C. tropicalis. The specificity of Sap of C. lusitaniae is most closely related to that of Sap of C. parapsilosis. We designed and prepared an inhibitor containing phenylstatine isoster that was equipotent towards all four proteases within the range of 10-10-10-9 M. The HIV-1 protease inhibitors ritonavir, saquinavir, indinavir, and nelfinavir were also tested for the inhibition of four Saps. Only ritonavir and saquinavir inhibited Sap2p, Sapt1p, Sapp1p, and Saplp in micromolar concentrations. |
| Databáze: | OpenAIRE |
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