Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of <i>Pelophylax kl. esculentus</i>, and Evaluation of Its Structure-Activity Relationships
Bacterial resistance against antibiotics has led to increasing numbers of treatment failures, and AMPs are widely accepted as becoming potential alternatives due to their advantages. Temporin-PKE is a novel peptide extracted from the skin secretion of <i>Pelophylax kl. esculentus</i> and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-05-01
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| Series: | Biomolecules |
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| Online Access: | https://www.mdpi.com/2218-273X/12/6/759 |
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| author | Yaxian Lin Yangyang Jiang Ziwei Zhao Yueyang Lu Xinping Xi Chengbang Ma Xiaoling Chen Mei Zhou Tianbao Chen Chris Shaw Lei Wang |
| author_facet | Yaxian Lin Yangyang Jiang Ziwei Zhao Yueyang Lu Xinping Xi Chengbang Ma Xiaoling Chen Mei Zhou Tianbao Chen Chris Shaw Lei Wang |
| author_sort | Yaxian Lin |
| collection | DOAJ |
| description | Bacterial resistance against antibiotics has led to increasing numbers of treatment failures, and AMPs are widely accepted as becoming potential alternatives due to their advantages. Temporin-PKE is a novel peptide extracted from the skin secretion of <i>Pelophylax kl. esculentus</i> and it displays a strong activity against Gram-positive bacteria, with an extreme cytotoxicity. Incorporating positively charged residues and introducing D-amino acids were the two main strategies adopted for the modifications. The transformation of the chirality of Ile could reduce haemolytic activity, and an analogue with appropriate D-isoforms could maintain antimicrobial activity and stability. The substitution of hydrophobic residues could bring about more potent and broad-spectrum antimicrobial activities. The analogues with Lys were less harmful to the normal cells and their stabilities remained at similarly high levels compared to temporin-PKE. The optimal number of charges was three, and the replacement on the polar face was a better choice. Temporin-PKE-3K exerted dually efficient functions includingstrong antimicrobial and anticancer activity. This analogue showed a reduced possibility for inducing resistance in MRSA and <i>Klebsiella pneumoniae</i>, a rather strong antimicrobial activity in vivo, and it exhibited the highest therapeutic index such that temporin-PKE-3K has the potential to be developed as a clinical drug. |
| first_indexed | 2024-03-10T00:18:53Z |
| format | Article |
| id | doaj.art-59e454d6a7db40409914068102c53099 |
| institution | Directory Open Access Journal |
| issn | 2218-273X |
| language | English |
| last_indexed | 2024-03-10T00:18:53Z |
| publishDate | 2022-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Biomolecules |
| spelling | doaj.art-59e454d6a7db40409914068102c530992023-11-23T15:46:25ZengMDPI AGBiomolecules2218-273X2022-05-0112675910.3390/biom12060759Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of <i>Pelophylax kl. esculentus</i>, and Evaluation of Its Structure-Activity RelationshipsYaxian Lin0Yangyang Jiang1Ziwei Zhao2Yueyang Lu3Xinping Xi4Chengbang Ma5Xiaoling Chen6Mei Zhou7Tianbao Chen8Chris Shaw9Lei Wang10School 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, 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, 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, UKBacterial resistance against antibiotics has led to increasing numbers of treatment failures, and AMPs are widely accepted as becoming potential alternatives due to their advantages. Temporin-PKE is a novel peptide extracted from the skin secretion of <i>Pelophylax kl. esculentus</i> and it displays a strong activity against Gram-positive bacteria, with an extreme cytotoxicity. Incorporating positively charged residues and introducing D-amino acids were the two main strategies adopted for the modifications. The transformation of the chirality of Ile could reduce haemolytic activity, and an analogue with appropriate D-isoforms could maintain antimicrobial activity and stability. The substitution of hydrophobic residues could bring about more potent and broad-spectrum antimicrobial activities. The analogues with Lys were less harmful to the normal cells and their stabilities remained at similarly high levels compared to temporin-PKE. The optimal number of charges was three, and the replacement on the polar face was a better choice. Temporin-PKE-3K exerted dually efficient functions includingstrong antimicrobial and anticancer activity. This analogue showed a reduced possibility for inducing resistance in MRSA and <i>Klebsiella pneumoniae</i>, a rather strong antimicrobial activity in vivo, and it exhibited the highest therapeutic index such that temporin-PKE-3K has the potential to be developed as a clinical drug.https://www.mdpi.com/2218-273X/12/6/759antimicrobial peptidestemporincationic amino acidsD-amino acidshaemolytic activity |
| spellingShingle | Yaxian Lin Yangyang Jiang Ziwei Zhao Yueyang Lu Xinping Xi Chengbang Ma Xiaoling Chen Mei Zhou Tianbao Chen Chris Shaw Lei Wang Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of <i>Pelophylax kl. esculentus</i>, and Evaluation of Its Structure-Activity Relationships Biomolecules antimicrobial peptides temporin cationic amino acids D-amino acids haemolytic activity |
| title | Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of <i>Pelophylax kl. esculentus</i>, and Evaluation of Its Structure-Activity Relationships |
| title_full | Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of <i>Pelophylax kl. esculentus</i>, and Evaluation of Its Structure-Activity Relationships |
| title_fullStr | Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of <i>Pelophylax kl. esculentus</i>, and Evaluation of Its Structure-Activity Relationships |
| title_full_unstemmed | Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of <i>Pelophylax kl. esculentus</i>, and Evaluation of Its Structure-Activity Relationships |
| title_short | Discovery of a Novel Antimicrobial Peptide, Temporin-PKE, from the Skin Secretion of <i>Pelophylax kl. esculentus</i>, and Evaluation of Its Structure-Activity Relationships |
| title_sort | discovery of a novel antimicrobial peptide temporin pke from the skin secretion of i pelophylax kl esculentus i and evaluation of its structure activity relationships |
| topic | antimicrobial peptides temporin cationic amino acids D-amino acids haemolytic activity |
| url | https://www.mdpi.com/2218-273X/12/6/759 |
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