A Thioether‐Stabilized d‐Proline–l‐Proline‐Induced β‐Hairpin Peptide of Defensin Segment Increases Its Anti‐Candida albicans Ability. (20th June 2016)

• Record Type: Journal Article
• Authors: Zhao, Bingchuan; Yang, Dan; Wong, Jack Ho; Wang, Jianpeng; Yin, Cuiming; Zhu, Yuxia; Fan, Shangrong; Ng, Tzi Bun; Xia, Jiang; Li, Zigang
• Is Part Of: Chembiochem. Volume 17:Number 15(2016)
• Page Start: 1416
• Page End: 1420
• Publication Date: 2016-06-20
• Subjects: antifungal agents -- beta-hairpin -- Candida albicans -- peptides -- thioether tether; Biochemistry -- Periodicals; Molecular biology -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1002/cbic.201600179
• Languages: English
• ISSNs: 1439-4227

Abstract

Abstract: We report a β‐hairpin dual stabilizing strategy: ad ‐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. Abstract : Using thed ‐Pro‐l ‐Pro dipeptide as the nucleating turn and a thioether tether as a side‐chain linkage can constrain peptides to the β‐hairpin conformation. We modified the C‐terminal β‐hairpin moiety of pv‐defensin, and obtained stabilized peptide with enhanced anti‐ C. albicans activity, high serum stability, and low hemolysis.