Peptide Dimerization as a Strategy for the Development of Antileishmanial Compounds
Leishmaniasis is recognized as a serious public health problem in Brazil and around the world. The limited availability of drugs for treatment, added to the diversity of side effects and the emergence of resistant strains, shows the importance of research focused on the development of new molecules,...
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MDPI AG
2024-10-01
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| author | Natália C. S. Coelho Deivys L. F. Portuondo Jhonatan Lima Angela M. A. Velásquez Valéria Valente Iracilda Z. Carlos Eduardo M. Cilli Márcia A. S. Graminha |
| author_facet | Natália C. S. Coelho Deivys L. F. Portuondo Jhonatan Lima Angela M. A. Velásquez Valéria Valente Iracilda Z. Carlos Eduardo M. Cilli Márcia A. S. Graminha |
| author_sort | Natália C. S. Coelho |
| collection | DOAJ |
| description | Leishmaniasis is recognized as a serious public health problem in Brazil and around the world. The limited availability of drugs for treatment, added to the diversity of side effects and the emergence of resistant strains, shows the importance of research focused on the development of new molecules, thus contributing to treatments. Therefore, this work aimed to identify leishmanicidal compounds using a peptide dimerization strategy, as well as to understand their mechanisms of action. Herein, it was demonstrated that the dimerization of the peptide TSHa, (TSHa)<sub>2</sub>K, presented higher potency and selectivity than its monomeric form when evaluated against <i>Leishmania mexicana</i> and <i>Leishmania amazonensis</i>. Furthermore, these compounds are capable of inhibiting the parasite cysteine protease, an important target explored for the development of antileishmanial compounds, as well as to selectively interact with the parasite membranes, as demonstrated by flow cytometry, permeabilization, and fluorescence microscopy experiments. Based on this, the identified molecules are candidates for use in in vivo studies with animal models to combat leishmaniasis. |
| format | Article |
| id | doaj-art-c1131fb19e3b4ffd8db6d0ae36f7b939 |
| institution | Kabale University |
| issn | 1420-3049 |
| language | English |
| publishDate | 2024-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj-art-c1131fb19e3b4ffd8db6d0ae36f7b9392024-11-08T14:38:34ZengMDPI AGMolecules1420-30492024-10-012921517010.3390/molecules29215170Peptide Dimerization as a Strategy for the Development of Antileishmanial CompoundsNatália C. S. Coelho0Deivys L. F. Portuondo1Jhonatan Lima2Angela M. A. Velásquez3Valéria Valente4Iracilda Z. Carlos5Eduardo M. Cilli6Márcia A. S. Graminha7Department of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilDepartment of Biochemistry and Organic Chemistry, Institute of Chemistry, São Paulo State University (UNESP), Araraquara 14800-060, SP, BrazilDepartment of Clinical Analysis, School of Pharmaceutical Sciences, São Paulo State University (UNESP), Araraquara 14800-903, SP, BrazilLeishmaniasis is recognized as a serious public health problem in Brazil and around the world. The limited availability of drugs for treatment, added to the diversity of side effects and the emergence of resistant strains, shows the importance of research focused on the development of new molecules, thus contributing to treatments. Therefore, this work aimed to identify leishmanicidal compounds using a peptide dimerization strategy, as well as to understand their mechanisms of action. Herein, it was demonstrated that the dimerization of the peptide TSHa, (TSHa)<sub>2</sub>K, presented higher potency and selectivity than its monomeric form when evaluated against <i>Leishmania mexicana</i> and <i>Leishmania amazonensis</i>. Furthermore, these compounds are capable of inhibiting the parasite cysteine protease, an important target explored for the development of antileishmanial compounds, as well as to selectively interact with the parasite membranes, as demonstrated by flow cytometry, permeabilization, and fluorescence microscopy experiments. Based on this, the identified molecules are candidates for use in in vivo studies with animal models to combat leishmaniasis.https://www.mdpi.com/1420-3049/29/21/5170dimerizationantimicrobial peptidesmembrane<i>Leishmania</i>TSHatemporin |
| spellingShingle | Natália C. S. Coelho Deivys L. F. Portuondo Jhonatan Lima Angela M. A. Velásquez Valéria Valente Iracilda Z. Carlos Eduardo M. Cilli Márcia A. S. Graminha Peptide Dimerization as a Strategy for the Development of Antileishmanial Compounds Molecules dimerization antimicrobial peptides membrane <i>Leishmania</i> TSHa temporin |
| title | Peptide Dimerization as a Strategy for the Development of Antileishmanial Compounds |
| title_full | Peptide Dimerization as a Strategy for the Development of Antileishmanial Compounds |
| title_fullStr | Peptide Dimerization as a Strategy for the Development of Antileishmanial Compounds |
| title_full_unstemmed | Peptide Dimerization as a Strategy for the Development of Antileishmanial Compounds |
| title_short | Peptide Dimerization as a Strategy for the Development of Antileishmanial Compounds |
| title_sort | peptide dimerization as a strategy for the development of antileishmanial compounds |
| topic | dimerization antimicrobial peptides membrane <i>Leishmania</i> TSHa temporin |
| url | https://www.mdpi.com/1420-3049/29/21/5170 |
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