Peptidomimetic inhibitors of extracellular aspartic proteinases of Candidaalbicans and Candida tropicalis

In an attempt to develop effective inhibitors of Candida secreted aspartic proteinases, we have prepared a series of N-protected peptides varying in t he type of scissile bond replacement, in the P and P' side chains as well a s in the N- and C-terminal modifications. The compounds were tested in vitr o with the chromogenic peptide substrate using purified secreted proteinase s of C. albicans and C. tropicalis. Our results have confirmed that the bin ding of inhibitors and their effectiveness is influenced by a number of enz yme-inhibitor interactions. Moreover, factors like solvation/desolvation co ntribute to the optimal binding energy of the inhibitors.