A Thioether-Stabilized d-Proline-l-Proline-Induced ß-Hairpin Peptide of Defensin Segment Increases Its Anti-Candida albicans Ability.

We report a ß-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 ß-hairpin. This method was used to modify the C-terminal ß-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.