A Thioether-Stabilized D-Proline-l-proline-induced Β-Hairpin Peptide of Defensin Segment Increases Its Anti-Candida Albicans Ability.

We report a beta-hairpin dual stabilizing strategy: a D-proline-lproline (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 beta-hairpin. This method was used to modify the C-terminal beta-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 mm), high serum stability (50% remaining after 48 h) and low hemolysis (< 10% at 152 mm). 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.