title: A Thioether-Stabilized d-Proline-l-Proline-Induced β-Hairpin Peptide of Defensin Segment Increases Its Anti-Candida albicans Ability.
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.
authors.affiliation: School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, 518055, China.
authors.forename: Bingchuan
authors.initials: B
authors.lastname: Zhao
authors.affiliation: School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, 518055, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Yang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Jack Ho
authors.initials: JH
authors.lastname: Wong
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Jianpeng
authors.initials: J
authors.lastname: Wang
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
authors.forename: Cuiming
authors.initials: C
authors.lastname: Yin
authors.affiliation: Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, 518036, China.
authors.forename: Yuxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Obstetrics and Gynecology, Peking University Shenzhen Hospital, Shenzhen, 518036, China. fanshangrong@21cn.com.
authors.forename: Shangrong
authors.initials: S
authors.lastname: Fan
authors.affiliation: School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. b021770@mailserv.cuhk.edu.hk.
authors.forename: Tzi Bun
authors.initials: TB
authors.lastname: Ng
authors.affiliation: Department of Chemistry, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China. jiangxia@cuhk.edu.hk.
authors.forename: Jiang
authors.initials: J
authors.lastname: Xia
authors.affiliation: School of Chemical Biology and Biotechnology, Shenzhen Graduate School of Peking University, Shenzhen, 518055, China. lizg@pkusz.edu.cn.
authors.forename: Zigang
authors.initials: Z
authors.lastname: Li
mesh_terms: D000935:Antifungal Agents / Q000737:chemistry* / Q000494:pharmacology; D002176:Candida albicans / Q000187:drug effects*; D041221:Candida glabrata / Q000187:drug effects; D023082:Defensins / Q000737:chemistry* / Q000494:pharmacology; D025141:Drug Resistance, Fungal / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D011392:Proline / Q000737:chemistry*; D055550:Protein Stability; D017433:Protein Structure, Secondary; D013329:Structure-Activity Relationship; D013440:Sulfides
chemical_list: D000935:Antifungal Agents; D023082:Defensins; D013440:Sulfides; D011392:Proline
keywords: Candida albicans; antifungal agents; beta-hairpin; peptides; thioether tether