Design, synthesis, and anti-tumor activities of novel Brevinin-1BYa peptidomimetics. (1st April 2021)

• Record Type: Journal Article
• Authors: Xiong, Shili; Wang, Nan; Liu, Chao; Shen, Huaxing; Qu, Zengqiang; Zhu, Lijun; Bai, Xiaosong; Hu, Hong-gang; Cong, Wei; Zhao, Liang
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 37(2021)
• Publication Date: 2021-04-01
• Subjects: Brevinin-1BYa -- Glyclopeptides -- Disulfide bond mimetics -- Anti-tumor activity; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2021.127831
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: Abstract: Brevinin-1BYa is an amphibian skin-derived peptide that exhibits promising anti-microbial activity against gram-positive and -negative bacteria. However, the anti-tumor activity of Brevinin-1BYa remains unclear, and, more importantly, its therapeutic application is limited owing to its poor protease and reduction stability. In this study, a series of novel Brevinin-1BYa derivatives, including O -linked N -acetyl-glucosamine glyclopeptides and disulfide bond mimetics, were designed and synthesized. Additionally, their anti-tumor activity against human prostate cancer cell line C4-2B, human NSCLC cell line A549 (adenocarcinoma), and human hepatoma cells line HuH-7 was investigated. Among these, the thioether bridge substituted peptidomimetic Brevinin-1BYa-3 displayed improved reduction stability, more stable secondary structure, greater protease stability, and increased anti-tumor activity compared with the original peptide, rendering it a promising leading compound for drug development, particularly for applications against malignant tumors.