Identification and Target-Modification of SL-BBI: A Novel Bowman–Birk Type Trypsin Inhibitor from <i>Sylvirana latouchii</i>
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...
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| Format: | Article |
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MDPI AG
2020-08-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/10/9/1254 |
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| author | Xi Chen Dong Chen Linyuan Huang Xiaoling Chen Mei Zhou Xinping Xi Chengbang Ma Tianbao Chen Lei Wang |
| author_facet | Xi Chen Dong Chen Linyuan Huang Xiaoling Chen Mei Zhou Xinping Xi Chengbang Ma Tianbao Chen Lei Wang |
| author_sort | Xi Chen |
| collection | DOAJ |
| description | 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 (<i>Sylvirana latouchii</i>) 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. |
| first_indexed | 2024-03-10T16:43:47Z |
| format | Article |
| id | doaj.art-52ae744e6d0a4419b33fa4783864a290 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T16:43:47Z |
| publishDate | 2020-08-01 |
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| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-52ae744e6d0a4419b33fa4783864a2902023-11-20T11:46:27ZengMDPI AGBiomolecules2218-273X2020-08-01109125410.3390/biom10091254Identification and Target-Modification of SL-BBI: A Novel Bowman–Birk Type Trypsin Inhibitor from <i>Sylvirana latouchii</i>Xi Chen0Dong Chen1Linyuan Huang2Xiaoling Chen3Mei Zhou4Xinping Xi5Chengbang Ma6Tianbao Chen7Lei Wang8Natural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKSchool of Life Sciences and Technology, China Pharmaceutical University, Nanjing 211198, ChinaNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKThe 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 (<i>Sylvirana latouchii</i>) 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.https://www.mdpi.com/2218-273X/10/9/1254natural moleculesBowman–Birk type inhibitorranacyclinantimicrobialanticancer |
| spellingShingle | Xi Chen Dong Chen Linyuan Huang Xiaoling Chen Mei Zhou Xinping Xi Chengbang Ma Tianbao Chen Lei Wang Identification and Target-Modification of SL-BBI: A Novel Bowman–Birk Type Trypsin Inhibitor from <i>Sylvirana latouchii</i> Biomolecules natural molecules Bowman–Birk type inhibitor ranacyclin antimicrobial anticancer |
| title | Identification and Target-Modification of SL-BBI: A Novel Bowman–Birk Type Trypsin Inhibitor from <i>Sylvirana latouchii</i> |
| title_full | Identification and Target-Modification of SL-BBI: A Novel Bowman–Birk Type Trypsin Inhibitor from <i>Sylvirana latouchii</i> |
| title_fullStr | Identification and Target-Modification of SL-BBI: A Novel Bowman–Birk Type Trypsin Inhibitor from <i>Sylvirana latouchii</i> |
| title_full_unstemmed | Identification and Target-Modification of SL-BBI: A Novel Bowman–Birk Type Trypsin Inhibitor from <i>Sylvirana latouchii</i> |
| title_short | Identification and Target-Modification of SL-BBI: A Novel Bowman–Birk Type Trypsin Inhibitor from <i>Sylvirana latouchii</i> |
| title_sort | identification and target modification of sl bbi a novel bowman birk type trypsin inhibitor from i sylvirana latouchii i |
| topic | natural molecules Bowman–Birk type inhibitor ranacyclin antimicrobial anticancer |
| url | https://www.mdpi.com/2218-273X/10/9/1254 |
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