Collect. Czech. Chem. Commun. 1999, 64, 130-137

Peptidomimetic Inhibitors of Extracellular Aspartic Proteinases of Candida albicans and Candida tropicalis

Kateřina Brožkováa, Ivana Křížováa, Libuše Pavlíčkováa, Martin Hradileka, Martin Fuseka, Tomáš Rumlb, Milan Součeka and Iva Pichováa,*

a Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, 166 10 Prague 6, Czech Republic
b Department of Biochemistry and Microbiology, Prague Institute of Chemical Technology, 166 28 Prague 6, Czech Republic


In an attempt to develop effective inhibitors of Candida secreted aspartic proteinases, we have prepared a series of N-protected peptides varying in the type of scissile bond replacement, in the P and P' side chains as well as in the N- and C-terminal modifications. The compounds were tested in vitro with the chromogenic peptide substrate using purified secreted proteinases of C. albicans and C. tropicalis. Our results have confirmed that the binding of inhibitors and their effectiveness is influenced by a number of enzyme-inhibitor interactions. Moreover, factors like solvation/desolvation contribute to the optimal binding energy of the inhibitors.

Keywords: Peptidomimetics; Peptides; Peptide bond isosteres; Secreted aspartic proteinases; Candida albicans; Candida tropicalis; Peptide inhibitors; Subsite specificity.