期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 27, 期 15, 页码 3586-3590出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2017.05.027
关键词
Dengue virus; Protease inhibitor; Cyclic peptide; Docking study; Antiviral activity
资金
- Creation of Innovation Centers for Advanced Interdisciplinary Research Areas Program
- Ministry of Education, Culture, Sports, Science, and Technology, Japan
- Shionogi
NS2B-NS3 protease is an essential enzyme for the replication of dengue virus (DENV), which continues to be a serious threat to worldwide public health. We designed and synthesized a series of cyclic peptides mimicking the substrates of this enzyme, and assayed their activity against the DENV-2 NS2B-NS3 protease. The introduction of aromatic residues at the appropriate positions and conformational restriction generated the most promising cyclic peptide with an IC50 of 0.95 mu M against NS2B-NS3 protease. Cyclic peptides with proper positioning of additional arginines and aromatic residues exhibited antiviral activity against DENV. Furthermore, replacing the C-terminal amide bond of the polybasic amino acid sequence with an amino methylene moiety stabilized the cyclic peptides against hydrolysis by NS2B-NS3 protease, while maintaining their enzyme inhibitory activity and antiviral activity. (C) 2017 Elsevier Ltd. All rights reserved.
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