A Thioether‐Stabilized d‐Proline–l‐Proline‐Induced β‐Hairpin Peptide of Defensin Segment Increases Its Anti‐Candida albicans Ability |
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| Authors: | Dr Bingchuan Zhao Dr Dan Yang Dr Jack Ho Wong Dr Jianpeng Wang Cuiming Yin Dr Yuxia Zhu Prof?Dr Shangrong Fan Prof?Dr Tzi Bun Ng Prof?Dr Jiang Xia Prof?Dr Zigang Li |
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| Affiliation: | 1. School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, China;2. School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China;3. Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China;4. Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, China |
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| Abstract: | 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. |
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| Keywords: | antifungal agents beta-hairpin Candida albicans peptides thioether tether |
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