Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities
Temporin family is one of the largest among antimicrobial peptides (AMPs), which act mainly by penetrating and disrupting the bacterial membranes. To further understand the relationship between the physical-chemical properties and their antimicrobial activity and selectivity, an analogue of Temporin...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Antibiotics |
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| Online Access: | https://www.mdpi.com/2079-6382/11/10/1285 |
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| author | Rosa Bellavita Elisabetta Buommino Bruno Casciaro Francesco Merlino Floriana Cappiello Noemi Marigliano Anella Saviano Francesco Maione Rosaria Santangelo Maria Luisa Mangoni Stefania Galdiero Paolo Grieco Annarita Falanga |
| author_facet | Rosa Bellavita Elisabetta Buommino Bruno Casciaro Francesco Merlino Floriana Cappiello Noemi Marigliano Anella Saviano Francesco Maione Rosaria Santangelo Maria Luisa Mangoni Stefania Galdiero Paolo Grieco Annarita Falanga |
| author_sort | Rosa Bellavita |
| collection | DOAJ |
| description | Temporin family is one of the largest among antimicrobial peptides (AMPs), which act mainly by penetrating and disrupting the bacterial membranes. To further understand the relationship between the physical-chemical properties and their antimicrobial activity and selectivity, an analogue of Temporin L, [Nle<sup>1</sup>, <span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL (Nle-Phe-Val-Pro-Trp-Phe-Lys-Phe-<span style="font-variant: small-caps;">d</span>Leu-<span style="font-variant: small-caps;">d</span>Lys-Arg-Ile-Leu-CONH<sub>2</sub>) has been developed in the present work. The design strategy consisted of the addition of a norleucine residue at the N-terminus of the lead peptide sequence, [<span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL, previously developed by our group. This modification promoted an increase of peptide hydrophobicity and, interestingly, more efficient activity against both Gram-positive and Gram-negative strains, without affecting human keratinocytes and red blood cells survival compared to the lead peptide. Thus, this novel compound was subjected to biophysical studies, which showed that the peptide [Nle<sup>1</sup>, <span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL is unstructured in water, while it adopts β-type conformation in liposomes mimicking bacterial membranes, in contrast to its lead peptide forming α-helical aggregates. After its aggregation in the bacterial membrane, [Nle<sup>1</sup>, <span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL induced membrane destabilization and deformation. In addition, the increase of peptide hydrophobicity did not cause a loss of anti-inflammatory activity of the peptide [Nle<sup>1</sup>, <span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL in comparison with its lead peptide. In this study, our results demonstrated that positive net charge, optimum hydrophobic−hydrophilic balance, and chain length remain the most important parameters to be addressed while designing small cationic AMPs. |
| first_indexed | 2024-03-09T20:51:01Z |
| format | Article |
| id | doaj.art-cf5b7be86c234404a635bcda627218ea |
| institution | Directory Open Access Journal |
| issn | 2079-6382 |
| language | English |
| last_indexed | 2024-03-09T20:51:01Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antibiotics |
| spelling | doaj.art-cf5b7be86c234404a635bcda627218ea2023-11-23T22:33:57ZengMDPI AGAntibiotics2079-63822022-09-011110128510.3390/antibiotics11101285Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory ActivitiesRosa Bellavita0Elisabetta Buommino1Bruno Casciaro2Francesco Merlino3Floriana Cappiello4Noemi Marigliano5Anella Saviano6Francesco Maione7Rosaria Santangelo8Maria Luisa Mangoni9Stefania Galdiero10Paolo Grieco11Annarita Falanga12Department of Pharmacy, University of Naples “Federico II”, Via Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Via Montesano 49, 80131 Naples, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Via Montesano 49, 80131 Naples, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Via Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Via Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Via Montesano 49, 80131 Naples, ItalyAlsa Lab SAS., Consorzio Fracta Labor Area PIP Lotto 25, Frattamaggiore, 80027 Naples, ItalyLaboratory Affiliated to Istituto Pasteur Italia-Fondazione Cenci Bolognetti, Department of Biochemical Sciences, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Via Montesano 49, 80131 Naples, ItalyDepartment of Pharmacy, University of Naples “Federico II”, Via Montesano 49, 80131 Naples, ItalyDepartment of Agricultural Science, University of Naples “Federico II”, 80055 Portici, ItalyTemporin family is one of the largest among antimicrobial peptides (AMPs), which act mainly by penetrating and disrupting the bacterial membranes. To further understand the relationship between the physical-chemical properties and their antimicrobial activity and selectivity, an analogue of Temporin L, [Nle<sup>1</sup>, <span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL (Nle-Phe-Val-Pro-Trp-Phe-Lys-Phe-<span style="font-variant: small-caps;">d</span>Leu-<span style="font-variant: small-caps;">d</span>Lys-Arg-Ile-Leu-CONH<sub>2</sub>) has been developed in the present work. The design strategy consisted of the addition of a norleucine residue at the N-terminus of the lead peptide sequence, [<span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL, previously developed by our group. This modification promoted an increase of peptide hydrophobicity and, interestingly, more efficient activity against both Gram-positive and Gram-negative strains, without affecting human keratinocytes and red blood cells survival compared to the lead peptide. Thus, this novel compound was subjected to biophysical studies, which showed that the peptide [Nle<sup>1</sup>, <span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL is unstructured in water, while it adopts β-type conformation in liposomes mimicking bacterial membranes, in contrast to its lead peptide forming α-helical aggregates. After its aggregation in the bacterial membrane, [Nle<sup>1</sup>, <span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL induced membrane destabilization and deformation. In addition, the increase of peptide hydrophobicity did not cause a loss of anti-inflammatory activity of the peptide [Nle<sup>1</sup>, <span style="font-variant: small-caps;">d</span>Leu<sup>9</sup>, <span style="font-variant: small-caps;">d</span>Lys<sup>10</sup>]TL in comparison with its lead peptide. In this study, our results demonstrated that positive net charge, optimum hydrophobic−hydrophilic balance, and chain length remain the most important parameters to be addressed while designing small cationic AMPs.https://www.mdpi.com/2079-6382/11/10/1285Temporin Lphysical-chemical propertypeptide hydrophobicityantimicrobial peptidesanti-inflammatory activity |
| spellingShingle | Rosa Bellavita Elisabetta Buommino Bruno Casciaro Francesco Merlino Floriana Cappiello Noemi Marigliano Anella Saviano Francesco Maione Rosaria Santangelo Maria Luisa Mangoni Stefania Galdiero Paolo Grieco Annarita Falanga Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities Antibiotics Temporin L physical-chemical property peptide hydrophobicity antimicrobial peptides anti-inflammatory activity |
| title | Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities |
| title_full | Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities |
| title_fullStr | Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities |
| title_full_unstemmed | Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities |
| title_short | Synthetic Amphipathic β-Sheet Temporin-Derived Peptide with Dual Antibacterial and Anti-Inflammatory Activities |
| title_sort | synthetic amphipathic β sheet temporin derived peptide with dual antibacterial and anti inflammatory activities |
| topic | Temporin L physical-chemical property peptide hydrophobicity antimicrobial peptides anti-inflammatory activity |
| url | https://www.mdpi.com/2079-6382/11/10/1285 |
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