Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients
Dermaseptins are an antimicrobial peptide family widely identified from the skin secretions of phyllomeudusinae frogs. Here, we identify Dermaseptin-PC (DM-PC), from the skin secretion of <i>Phyllomedusa coelestis</i>, and further investigate the properties of this peptide, and a number...
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| Format: | Article |
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MDPI AG
2019-10-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/9/11/646 |
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| author | Yuan Ying Hui Wang Xinping Xi Chengbang Ma Yue Liu Mei Zhou Qiang Du James F. Burrows Minjie Wei Tianbao Chen Lei Wang |
| author_facet | Yuan Ying Hui Wang Xinping Xi Chengbang Ma Yue Liu Mei Zhou Qiang Du James F. Burrows Minjie Wei Tianbao Chen Lei Wang |
| author_sort | Yuan Ying |
| collection | DOAJ |
| description | Dermaseptins are an antimicrobial peptide family widely identified from the skin secretions of phyllomeudusinae frogs. Here, we identify Dermaseptin-PC (DM-PC), from the skin secretion of <i>Phyllomedusa coelestis</i>, and further investigate the properties of this peptide, and a number of rationally designed truncated derivatives. The truncated 19-mer derived from the N-terminus exhibited similar antimicrobial potency when compared to the parent peptide, but the haemolytic effect of this truncated peptide was significantly decreased. Based on previous studies, the charge and hydrophobicity of truncated derivatives can affect the bioactivity of these peptides and thus we designed a 10-mer derivative with an optimised positive charge and a cyclohexylalanine (Cha) at the C-terminus for enhancing the hydrophobicity, DMPC-10A, which retained the antimicrobial activity of the parent peptide. To further investigate the influence of Cha at the C-terminus on activity, it was substituted by alanine (Ala) to generate another derivative, DMPC-10, but this was found to be much less potent. In addition, DM-PC, DMPC-19 and DMPC-10A not only rapidly killed planktonic bacteria isolated from cystic fibrosis (CF) patient, but also effectively eradicated their biofilm matrices. |
| first_indexed | 2024-12-13T02:40:20Z |
| format | Article |
| id | doaj.art-47fc246af9b2431b9738154a0dd2825b |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-12-13T02:40:20Z |
| publishDate | 2019-10-01 |
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| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-47fc246af9b2431b9738154a0dd2825b2022-12-22T00:02:19ZengMDPI AGBiomolecules2218-273X2019-10-0191164610.3390/biom9110646biom9110646Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis PatientsYuan Ying0Hui Wang1Xinping Xi2Chengbang Ma3Yue Liu4Mei Zhou5Qiang Du6James F. Burrows7Minjie Wei8Tianbao Chen9Lei Wang10School of Pharmacy, China Medical University, Shenyang 110001, ChinaSchool of Pharmacy, China Medical University, Shenyang 110001, ChinaNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKSchool of Pharmacy, China Medical University, Shenyang 110001, ChinaNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKSchool of Pharmacy, China Medical University, Shenyang 110001, ChinaNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKNatural Drug Discovery Group, School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, Northern Ireland, UKDermaseptins are an antimicrobial peptide family widely identified from the skin secretions of phyllomeudusinae frogs. Here, we identify Dermaseptin-PC (DM-PC), from the skin secretion of <i>Phyllomedusa coelestis</i>, and further investigate the properties of this peptide, and a number of rationally designed truncated derivatives. The truncated 19-mer derived from the N-terminus exhibited similar antimicrobial potency when compared to the parent peptide, but the haemolytic effect of this truncated peptide was significantly decreased. Based on previous studies, the charge and hydrophobicity of truncated derivatives can affect the bioactivity of these peptides and thus we designed a 10-mer derivative with an optimised positive charge and a cyclohexylalanine (Cha) at the C-terminus for enhancing the hydrophobicity, DMPC-10A, which retained the antimicrobial activity of the parent peptide. To further investigate the influence of Cha at the C-terminus on activity, it was substituted by alanine (Ala) to generate another derivative, DMPC-10, but this was found to be much less potent. In addition, DM-PC, DMPC-19 and DMPC-10A not only rapidly killed planktonic bacteria isolated from cystic fibrosis (CF) patient, but also effectively eradicated their biofilm matrices.https://www.mdpi.com/2218-273X/9/11/646antimicrobial peptidedermaseptinpeptide designcystic fibrosis infection |
| spellingShingle | Yuan Ying Hui Wang Xinping Xi Chengbang Ma Yue Liu Mei Zhou Qiang Du James F. Burrows Minjie Wei Tianbao Chen Lei Wang Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients Biomolecules antimicrobial peptide dermaseptin peptide design cystic fibrosis infection |
| title | Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients |
| title_full | Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients |
| title_fullStr | Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients |
| title_full_unstemmed | Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients |
| title_short | Design of N-Terminal Derivatives from a Novel Dermaseptin Exhibiting Broad-Spectrum Antimicrobial Activity against Isolates from Cystic Fibrosis Patients |
| title_sort | design of n terminal derivatives from a novel dermaseptin exhibiting broad spectrum antimicrobial activity against isolates from cystic fibrosis patients |
| topic | antimicrobial peptide dermaseptin peptide design cystic fibrosis infection |
| url | https://www.mdpi.com/2218-273X/9/11/646 |
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