In Vitro & In Vivo Studies on Identifying and Designing Temporin-1CEh from the Skin Secretion of <i>Rana chensinensis</i> as the Optimised Antibacterial Prototype Drug
Amphibian skin secretion is an ideal source of antimicrobial peptides that are difficult to induce drug resistance to due to their membrane-targeting mechanism as a new treatment scheme. In this study, a natural antimicrobial peptide Temporin-1CEh was identified by molecular cloning and mass spectro...
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| Format: | Article |
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MDPI AG
2022-03-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/14/3/604 |
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| author | Zhuming Ye Xiaowei Zhou Xinping Xi Yu Zai Mei Zhou Xiaoling Chen Chengbang Ma Tianbao Chen Lei Wang Hang Fai Kwok |
| author_facet | Zhuming Ye Xiaowei Zhou Xinping Xi Yu Zai Mei Zhou Xiaoling Chen Chengbang Ma Tianbao Chen Lei Wang Hang Fai Kwok |
| author_sort | Zhuming Ye |
| collection | DOAJ |
| description | Amphibian skin secretion is an ideal source of antimicrobial peptides that are difficult to induce drug resistance to due to their membrane-targeting mechanism as a new treatment scheme. In this study, a natural antimicrobial peptide Temporin-1CEh was identified by molecular cloning and mass spectrometry from the skin secretions of the Chinese forest frog (<i>Rana chensinensis</i>). Through the study of the structure and biological activity, it was found that Temporin-1CEh was a helical peptide from the Temporin family, and possessed good anti-Gram-positive bacteria activity through the mechanism of membrane destruction. Seven analogues were further designed to obtain broad-spectrum antimicrobial activity and higher stability in different physiological conditions. The results showed that T1CEh-KKPWW showed potent antibacterial activity with significantly increasing the activity against Gram-negative bacteria in vitro and in vivo with low haemolysis. In addition, T1CEh-KKPWW2 showed high sensitivity to the pH, serum or salts conditions, which applied a branched structure to allow the active units of the peptide to accumulate. Even though the haemolytic activity was increased, the stable antibacterial activity made this novel analogue meet the conditions to become a potential candidate in future antimicrobial and antibiofilm applications. |
| first_indexed | 2024-03-09T12:58:40Z |
| format | Article |
| id | doaj.art-443a7971bbdd42fb831a1e8683626cf2 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-09T12:58:40Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-443a7971bbdd42fb831a1e8683626cf22023-11-30T21:57:17ZengMDPI AGPharmaceutics1999-49232022-03-0114360410.3390/pharmaceutics14030604In Vitro & In Vivo Studies on Identifying and Designing Temporin-1CEh from the Skin Secretion of <i>Rana chensinensis</i> as the Optimised Antibacterial Prototype DrugZhuming Ye0Xiaowei Zhou1Xinping Xi2Yu Zai3Mei Zhou4Xiaoling Chen5Chengbang Ma6Tianbao Chen7Lei Wang8Hang Fai Kwok9Institute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaInstitute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaInstitute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaInstitute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaSchool of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UKInstitute of Translational Medicine, Faculty of Health Sciences, University of Macau, Taipa, Macau SAR 999078, ChinaAmphibian skin secretion is an ideal source of antimicrobial peptides that are difficult to induce drug resistance to due to their membrane-targeting mechanism as a new treatment scheme. In this study, a natural antimicrobial peptide Temporin-1CEh was identified by molecular cloning and mass spectrometry from the skin secretions of the Chinese forest frog (<i>Rana chensinensis</i>). Through the study of the structure and biological activity, it was found that Temporin-1CEh was a helical peptide from the Temporin family, and possessed good anti-Gram-positive bacteria activity through the mechanism of membrane destruction. Seven analogues were further designed to obtain broad-spectrum antimicrobial activity and higher stability in different physiological conditions. The results showed that T1CEh-KKPWW showed potent antibacterial activity with significantly increasing the activity against Gram-negative bacteria in vitro and in vivo with low haemolysis. In addition, T1CEh-KKPWW2 showed high sensitivity to the pH, serum or salts conditions, which applied a branched structure to allow the active units of the peptide to accumulate. Even though the haemolytic activity was increased, the stable antibacterial activity made this novel analogue meet the conditions to become a potential candidate in future antimicrobial and antibiofilm applications.https://www.mdpi.com/1999-4923/14/3/604antimicrobial activitytemporinbranched peptide<i>Galleria mellonella</i> larva model |
| spellingShingle | Zhuming Ye Xiaowei Zhou Xinping Xi Yu Zai Mei Zhou Xiaoling Chen Chengbang Ma Tianbao Chen Lei Wang Hang Fai Kwok In Vitro & In Vivo Studies on Identifying and Designing Temporin-1CEh from the Skin Secretion of <i>Rana chensinensis</i> as the Optimised Antibacterial Prototype Drug Pharmaceutics antimicrobial activity temporin branched peptide <i>Galleria mellonella</i> larva model |
| title | In Vitro & In Vivo Studies on Identifying and Designing Temporin-1CEh from the Skin Secretion of <i>Rana chensinensis</i> as the Optimised Antibacterial Prototype Drug |
| title_full | In Vitro & In Vivo Studies on Identifying and Designing Temporin-1CEh from the Skin Secretion of <i>Rana chensinensis</i> as the Optimised Antibacterial Prototype Drug |
| title_fullStr | In Vitro & In Vivo Studies on Identifying and Designing Temporin-1CEh from the Skin Secretion of <i>Rana chensinensis</i> as the Optimised Antibacterial Prototype Drug |
| title_full_unstemmed | In Vitro & In Vivo Studies on Identifying and Designing Temporin-1CEh from the Skin Secretion of <i>Rana chensinensis</i> as the Optimised Antibacterial Prototype Drug |
| title_short | In Vitro & In Vivo Studies on Identifying and Designing Temporin-1CEh from the Skin Secretion of <i>Rana chensinensis</i> as the Optimised Antibacterial Prototype Drug |
| title_sort | in vitro in vivo studies on identifying and designing temporin 1ceh from the skin secretion of i rana chensinensis i as the optimised antibacterial prototype drug |
| topic | antimicrobial activity temporin branched peptide <i>Galleria mellonella</i> larva model |
| url | https://www.mdpi.com/1999-4923/14/3/604 |
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