We report a β-hairpin dual stabilizing strategy: a d-proline-l-proline (d-Pro-l-Pro) dipeptide as the nucleating turn, and a thioether tether as a side-chain linkage at a precisely designed position to stabilize the β-hairpin. This method was used to modify the C-terminal β-hairpin moiety of the plant defensin, pv-defensin, in order to obtain a stabilized peptide with enhanced anti-Candida albicans activity (MIC 84-3.0 μm), high serum stability (50 % remaining after 48 h) and low hemolysis (<10 % at 152 μm). This modified peptide penetrated the C. albicans cell membrane within 5 min and showed high activity against clinically isolated antibiotic-resistant C. albicans and Candida glabrata strains.
Keywords: Candida albicans; antifungal agents; beta-hairpin; peptides; thioether tether.
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