An effective modification strategy to build multifunctional peptides based on a trypsin inhibitory peptide of the Kunitz family

Ying Wang, Daning Shi, Wanchen Zou, Yangyang Jiang, Tao Wang, Xiaoling Chen, Chengbang Ma, Wei Li, Tianbao Chen, Lei Wang, Mei Zhou

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Abstract

Peptides with antimicrobial activity or protease inhibitory activity are potential candidates to supplement traditional antibiotics or cancer chemotherapies. However, the potential of many peptides are limited by drawbacks such as cytotoxicity or susceptibility to hydrolysis. Therefore, strategies to modify the structure of promising peptides may represent an effective approach for developing more promising clinical candidates. In this study, the mature peptide OSTI−1949, a Kunitz-type inhibitor from Odorrana schmackeri, and four designed analogues were successfully synthesised. In contrast to the parent peptide, the analogues showed impressive multi-functionality including antimicrobial, anticancer, and trypsin inhibitory activities. In terms of safety, there were no obvious changes observed in the haemolytic activity at the highest tested concentration, and the analogue OSTI−2461 showed an increase in activity against cancer cell lines without cytotoxicity to normal cells (HaCaT). In summary, through structural modification of a natural Kunitz-type peptide, the biological activity of analogues was improved whilst retaining low cytotoxicity. The strategy of helicity enhancement by forming an artificial α-helix and ß-sheet structure provides a promising way to develop original bioactive peptides for clinical therapeutics.
Original languageEnglish
Article number597
JournalPharmaceutics
Volume16
Issue number5
Early online date27 Apr 2024
DOIs
Publication statusPublished - May 2024

Keywords

  • Kunitz-type peptides; multifunctional peptides; secondary structure; antimicrobial activity in vitro and in vivo; antiproliferative activity; apoptosis

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