ACS Chemical Biology p. 516 - 525 (2019)
Update date:2022-08-24
Topics:
Li, Yulei
Zhang, Yihan
Wu, Minghao
Chang, Qi
Hu, Honggang
Zhao, Xia
As a host defense peptide, hymenochirin-1B has attracted increasing attention for its strong cytotoxic activities. However, its poor selectivity and proteolytic stability remain major obstacles for clinical application. To solve these problems, we designed and synthesized a series of peptide analogues of hymenochirin-1B based on cationic residue substitution and stapling combined with a glycosylation strategy. Some analogues showed improvement not only in selectivity and proteolytic stability but also in antitumor activity. Among them, the glycosylated stapled peptide H-58 was identified as the most potential antitumor peptide. Flow cytometry and a competitive binding assay revealed that H-58 displayed significant antitumor selectivity. Confocal microscopy and nuclear staining with Hoechst dye demonstrated that H-58 entered the nucleus and caused DNA damage. In summary, the strategy of glycosylated stapled peptides is a promising approach for improving the antitumor selectivity, proteolytic stability, and antitumor activity of hymenochirin-1B, which can be used for other bioactive peptide modifications.
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