Abstract
The peptides from the ranacyclin family share similar active disulphide loop with plant-derived Bowman–Birk type inhibitors, some of which have the dual activities of trypsin inhibition and antimicrobial. Herein, a novel Bowman–Birk type trypsin inhibitor of the ranacyclin family was identified from the skin secretion of broad-folded frog (Sylvirana latouchii) by molecular cloning method and named as SL-BBI. After chemical synthesis, it was proved to be a potent inhibitor of trypsin with a Ki value of 230.5 nM and showed weak antimicrobial activity against tested microorganisms. Modified analogue K-SL maintains the original inhibitory activity with a Ki value of 77.27 nM while enhancing the antimicrobial activity. After the substitution of active P1 site to phenylalanine and P2′ site to isoleucine, F-SL regenerated its inhibitory activity on chymotrypsin with a Ki value of 309.3 nM and exhibited antiproliferative effects on PC-3, MCF-7 and a series of non-small cell lung cancer cell lines without cell membrane damage. The affinity of F-SL for the β subunits in the yeast 20S proteasome showed by molecular docking simulations enriched the understanding of the possible action mode of Bowman–Birk type inhibitors. Further mechanistic studies have shown that F-SL can activate caspase 3/7 in H157 cells and induce apoptosis, which means it has the potential to become an anticancer agent.
Original language | English |
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Pages (from-to) | 1-20 |
Number of pages | 20 |
Journal | Biomolecules |
Volume | 10 |
Issue number | 9 |
DOIs | |
Publication status | Published - 28 Aug 2020 |
Keywords
- anticancer
- antimicrobial
- Bowman–Birk type inhibitor
- natural molecules
- ranacyclin
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
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Student Theses
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Identification and rational design of Bowman-Birk type protease inhibitory peptides derived from Ranidae frogs
Author: Chen, X., Dec 2020Supervisor: Zhou, M. (Supervisor), Wang, L. (Supervisor), Ma, C. (Supervisor) & Chen, T. (Supervisor)
Student thesis: Doctoral Thesis › Doctor of Philosophy