Design, synthesis, and biological evaluation of stapled ascaphin-8 peptides

Jing Liu; Si Chen; Xiao-Yun Chai; Fei Gao; Chen Wang; Hua Tang; Xiang Li; Ying Liu; Hong-Gang Hu

doi:10.1016/j.bmc.2021.116158

Design, synthesis, and biological evaluation of stapled ascaphin-8 peptides

Bioorg Med Chem. 2021 Jun 15:40:116158. doi: 10.1016/j.bmc.2021.116158. Epub 2021 Apr 22.

Authors

Jing Liu¹, Si Chen², Xiao-Yun Chai³, Fei Gao⁴, Chen Wang⁵, Hua Tang⁶, Xiang Li⁷, Ying Liu⁸, Hong-Gang Hu⁹

Affiliations

¹ Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. Electronic address: liuJing96@shu.edu.cn.
² School of Medicine, Shanghai University, Shanghai 200444, China. Electronic address: Caroline-sisi-chen@hotmail.com.
³ School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: chaixy1207@163.com.
⁴ Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. Electronic address: 14b307010@hit.edu.cn.
⁵ Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. Electronic address: wangchen02@shu.edu.cn.
⁶ Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. Electronic address: tanghua0309@shu.edu.cn.
⁷ School of Pharmacy, Second Military Medical University, Shanghai 200433, China. Electronic address: xiangli@smmu.edu.cn.
⁸ Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. Electronic address: liuying1984@shu.edu.cn.
⁹ Institute of Translational Medicine, Shanghai University, Shanghai 200444, China. Electronic address: hhu66@shu.edu.cn.

PMID: 33932712
DOI: 10.1016/j.bmc.2021.116158

Abstract

Ascaphin-8 is an α-helical anti-tumor and antimicrobial peptide containing 19 residues, which was isolated from norepinephrine-stimulated skin secretions of the North American tailed frog Ascaphus truei. To improve both its stability and biological activities, a series of hydrocarbon-stapled analogs of Ascaphin-8 were synthesized and investigated for their potential antiproliferative activities. The activity studies were evaluated using the CCK-8 method and colony formation assay on human cancer cell lines. Ascaphin-8-3, as the most active peptide, showed a stronger inhibition effect when compared with the parent peptide for the tested cell lines. In addition, the effect of Ascaphin-8-3 on inhibiting the metastatic capabilities of A549 cells was more powerful than that of the parent peptide. This peptide derivative showed potentiality for further optimization in antitumor drugs.

Keywords: AMP; Anti-tumor; Ascaphin-8; Stapled peptide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antimicrobial Cationic Peptides / chemical synthesis
Antimicrobial Cationic Peptides / chemistry
Antimicrobial Cationic Peptides / pharmacology*
Cell Movement / drug effects
Cell Survival / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Drug Design*
Humans
Molecular Structure
Structure-Activity Relationship

Substances

Antimicrobial Cationic Peptides
ascaphin-8 peptide, Ascaphus truei