Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates
DMPC-10A (ALWKKLLKK-Cha-NH<sub>2</sub>) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/9/9/627 |
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| author | Yu Zai Yuan Ying Zhuming Ye Mei Zhou Chengbang Ma Zhanzhong Shi Xiaoling Chen Xinping Xi Tianbao Chen Lei Wang |
| author_facet | Yu Zai Yuan Ying Zhuming Ye Mei Zhou Chengbang Ma Zhanzhong Shi Xiaoling Chen Xinping Xi Tianbao Chen Lei Wang |
| author_sort | Yu Zai |
| collection | DOAJ |
| description | DMPC-10A (ALWKKLLKK-Cha-NH<sub>2</sub>) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala<sup>1</sup> and Trp<sup>3</sup> remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and <i>Klebsiella pneumoniae</i> using the <i>Galleria mellonella</i> larva model and displayed synergistic activities with gentamicin against carbapenem-resistant <i>K. pneumoniae</i> strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens. |
| first_indexed | 2024-03-10T16:09:17Z |
| format | Article |
| id | doaj.art-00aa02958f1a464e81d6dd35656f6004 |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-10T16:09:17Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-00aa02958f1a464e81d6dd35656f60042023-11-20T14:33:02ZengMDPI AGAntibiotics2079-63822020-09-019962710.3390/antibiotics9090627Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin TruncatesYu Zai0Yuan Ying1Zhuming Ye2Mei Zhou3Chengbang Ma4Zhanzhong Shi5Xiaoling Chen6Xinping Xi7Tianbao Chen8Lei Wang9School of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKDepartment of Natural Sciences, Faculty of Science and Technology, Middlesex University, London NW4 4BT, UKSchool of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKSchool of Pharmacy, Queen’s University Belfast, Belfast BT9 7BL, UKDMPC-10A (ALWKKLLKK-Cha-NH<sub>2</sub>) is a 10-mer peptide derivative from the N-terminal domain of Dermaseptin-PC which has shown broad-spectrum antimicrobial activity as well as a considerable hemolytic effect. In order to reduce hemolytic activity and improve stability to endogenous enzymes, a D-amino acid enantiomer (DMPC-10B) was designed by substituting all L-Lys and L-Leu with their respective D-form amino acid residues, while the Ala<sup>1</sup> and Trp<sup>3</sup> remained unchanged. The D-amino acid enantiomer exhibited similar antimicrobial potency to the parent peptide but exerted lower cytotoxicity and hemolytic activity. Meanwhile, DMPC-10B exhibited remarkable resistance to hydrolysis by trypsin and chymotrypsin. In addition to these advantages, DMPC-10B exhibited an outstanding antibacterial effect against Methicillin-resistant <i>Staphylococcus aureus</i> (MRSA) and <i>Klebsiella pneumoniae</i> using the <i>Galleria mellonella</i> larva model and displayed synergistic activities with gentamicin against carbapenem-resistant <i>K. pneumoniae</i> strains. This indicates that DMPC-10B would be a promising alternative for treating antibiotic-resistant pathogens.https://www.mdpi.com/2079-6382/9/9/627antimicrobial peptideD-amino acidprotease stability<i>Galleria mellonella</i> larva model |
| spellingShingle | Yu Zai Yuan Ying Zhuming Ye Mei Zhou Chengbang Ma Zhanzhong Shi Xiaoling Chen Xinping Xi Tianbao Chen Lei Wang Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates Antibiotics antimicrobial peptide D-amino acid protease stability <i>Galleria mellonella</i> larva model |
| title | Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates |
| title_full | Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates |
| title_fullStr | Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates |
| title_full_unstemmed | Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates |
| title_short | Broad-Spectrum Antimicrobial Activity and Improved Stability of a D-Amino Acid Enantiomer of DMPC-10A, the Designed Derivative of Dermaseptin Truncates |
| title_sort | broad spectrum antimicrobial activity and improved stability of a d amino acid enantiomer of dmpc 10a the designed derivative of dermaseptin truncates |
| topic | antimicrobial peptide D-amino acid protease stability <i>Galleria mellonella</i> larva model |
| url | https://www.mdpi.com/2079-6382/9/9/627 |
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