Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptide
FR235222 is a natural tetra-cyclopeptide with a strong inhibition effect on histone deacetylases, effective on mammalian cells as well as on intracellular apicomplexan parasites, such as Toxoplasma gondii, in the tachyzoite and bradyzoite stages. This molecule is characterized by two parts: the zinc...
| Autores: | , , , , , , , , , , |
|---|---|
| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2021 |
| País: | Brasil |
| Institución: | Universidade Federal de Minas Gerais (UFMG) |
| Repositorio: | Repositório Institucional da UFMG |
| Idioma: | inglés |
| OAI Identifier: | oai:repositorio.ufmg.br:1843/73163 |
| Acceso en línea: | https://doi.org/10.3390/molecules26247506 http://hdl.handle.net/1843/73163 https://orcid.org/0000-0002-5843-0842 https://orcid.org/0000-0001-8547-6021 https://orcid.org/0000-0002-0784-6450 https://orcid.org/0000-0001-6974-3724 https://orcid.org/0000-0002-1480-4451 https://orcid.org/0000-0002-9080-7638 https://orcid.org/0000-0003-1038-9681 |
| Access Level: | acceso abierto |
| Palabra clave: | Cyclopeptides Histone deacetylase Toxoplasma gondii Bradyzoite Cell-permeable agent Molecular dynamics Dinâmica molecular Peptídios Moléculas |
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Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptideCyclopeptidesHistone deacetylaseToxoplasma gondiiBradyzoiteCell-permeable agentMolecular dynamicsToxoplasma gondiiDinâmica molecularPeptídiosMoléculasFR235222 is a natural tetra-cyclopeptide with a strong inhibition effect on histone deacetylases, effective on mammalian cells as well as on intracellular apicomplexan parasites, such as Toxoplasma gondii, in the tachyzoite and bradyzoite stages. This molecule is characterized by two parts: the zinc-binding group, responsible for the binding to the histone deacetylase, and the cyclic tetrapeptide moiety, which plays a crucial role in cell permeability. Recently, we have shown that the cyclic tetrapeptide coupled with a fluorescent diethyl-amino-coumarin was able to maintain properties of cellular penetration on human cells. Here, we show that this property can be extended to the crossing of the Toxoplasma gondii cystic cell wall and the cell membrane of the parasite in its bradyzoite form, while maintaining a high efficacy as a histone deacetylase inhibitor. The investigation by molecular modeling allows a better understanding of the penetration mechanism.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoFAPEMIG - Fundação de Amparo à Pesquisa do Estado de Minas GeraisCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorOutra AgênciaUniversidade Federal de Minas GeraisBrasilICX - DEPARTAMENTO DE QUÍMICAUFMG2024-08-06T23:05:03Z2024-08-06T23:05:03Z2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlepdfapplication/pdfhttps://doi.org/10.3390/molecules262475061420-3049http://hdl.handle.net/1843/73163https://orcid.org/0000-0002-5843-0842https://orcid.org/0000-0001-8547-6021https://orcid.org/0000-0002-0784-6450https://orcid.org/0000-0001-6974-3724https://orcid.org/0000-0002-1480-4451https://orcid.org/0000-0002-9080-7638https://orcid.org/0000-0003-1038-9681engMoleculesinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UFMGinstname:Universidade Federal de Minas Gerais (UFMG)instacron:UFMGCéline DardBaptiste LeforestierFlaviane Francisco HilárioMohamed Dit Mady TraoréMarie-Ange LespinasseBasile PérèsMarie-Carmen MolinaRossimiriam Pereira de FreitasAnne MiletDanièle MaubonYung-Sing Wong2024-08-06T23:05:03Zoai:repositorio.ufmg.br:1843/73163Repositório InstitucionalPUBhttps://repositorio.ufmg.br/oairepositorio@ufmg.bropendoar:2024-08-06T23:05:03Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG)false |
| dc.title.none.fl_str_mv |
Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptide |
| title |
Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptide |
| spellingShingle |
Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptide Céline Dard Cyclopeptides Histone deacetylase Toxoplasma gondii Bradyzoite Cell-permeable agent Molecular dynamics Toxoplasma gondii Dinâmica molecular Peptídios Moléculas |
| title_short |
Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptide |
| title_full |
Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptide |
| title_fullStr |
Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptide |
| title_full_unstemmed |
Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptide |
| title_sort |
Crossing of the cystic barriers of Toxoplasma gondii by the fluorescent coumarin tetra-cyclopeptide |
| dc.creator.none.fl_str_mv |
Céline Dard Baptiste Leforestier Flaviane Francisco Hilário Mohamed Dit Mady Traoré Marie-Ange Lespinasse Basile Pérès Marie-Carmen Molina Rossimiriam Pereira de Freitas Anne Milet Danièle Maubon Yung-Sing Wong |
| author |
Céline Dard |
| author_facet |
Céline Dard Baptiste Leforestier Flaviane Francisco Hilário Mohamed Dit Mady Traoré Marie-Ange Lespinasse Basile Pérès Marie-Carmen Molina Rossimiriam Pereira de Freitas Anne Milet Danièle Maubon Yung-Sing Wong |
| author_role |
author |
| author2 |
Baptiste Leforestier Flaviane Francisco Hilário Mohamed Dit Mady Traoré Marie-Ange Lespinasse Basile Pérès Marie-Carmen Molina Rossimiriam Pereira de Freitas Anne Milet Danièle Maubon Yung-Sing Wong |
| author2_role |
author author author author author author author author author author |
| dc.subject.por.fl_str_mv |
Cyclopeptides Histone deacetylase Toxoplasma gondii Bradyzoite Cell-permeable agent Molecular dynamics Toxoplasma gondii Dinâmica molecular Peptídios Moléculas |
| topic |
Cyclopeptides Histone deacetylase Toxoplasma gondii Bradyzoite Cell-permeable agent Molecular dynamics Toxoplasma gondii Dinâmica molecular Peptídios Moléculas |
| description |
FR235222 is a natural tetra-cyclopeptide with a strong inhibition effect on histone deacetylases, effective on mammalian cells as well as on intracellular apicomplexan parasites, such as Toxoplasma gondii, in the tachyzoite and bradyzoite stages. This molecule is characterized by two parts: the zinc-binding group, responsible for the binding to the histone deacetylase, and the cyclic tetrapeptide moiety, which plays a crucial role in cell permeability. Recently, we have shown that the cyclic tetrapeptide coupled with a fluorescent diethyl-amino-coumarin was able to maintain properties of cellular penetration on human cells. Here, we show that this property can be extended to the crossing of the Toxoplasma gondii cystic cell wall and the cell membrane of the parasite in its bradyzoite form, while maintaining a high efficacy as a histone deacetylase inhibitor. The investigation by molecular modeling allows a better understanding of the penetration mechanism. |
| publishDate |
2021 |
| dc.date.none.fl_str_mv |
2021 2024-08-06T23:05:03Z 2024-08-06T23:05:03Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
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article |
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publishedVersion |
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https://doi.org/10.3390/molecules26247506 1420-3049 http://hdl.handle.net/1843/73163 https://orcid.org/0000-0002-5843-0842 https://orcid.org/0000-0001-8547-6021 https://orcid.org/0000-0002-0784-6450 https://orcid.org/0000-0001-6974-3724 https://orcid.org/0000-0002-1480-4451 https://orcid.org/0000-0002-9080-7638 https://orcid.org/0000-0003-1038-9681 |
| url |
https://doi.org/10.3390/molecules26247506 http://hdl.handle.net/1843/73163 https://orcid.org/0000-0002-5843-0842 https://orcid.org/0000-0001-8547-6021 https://orcid.org/0000-0002-0784-6450 https://orcid.org/0000-0001-6974-3724 https://orcid.org/0000-0002-1480-4451 https://orcid.org/0000-0002-9080-7638 https://orcid.org/0000-0003-1038-9681 |
| identifier_str_mv |
1420-3049 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Molecules |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
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openAccess |
| dc.format.none.fl_str_mv |
pdf application/pdf |
| dc.publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais Brasil ICX - DEPARTAMENTO DE QUÍMICA UFMG |
| publisher.none.fl_str_mv |
Universidade Federal de Minas Gerais Brasil ICX - DEPARTAMENTO DE QUÍMICA UFMG |
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reponame:Repositório Institucional da UFMG instname:Universidade Federal de Minas Gerais (UFMG) instacron:UFMG |
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Universidade Federal de Minas Gerais (UFMG) |
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UFMG |
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UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG |
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Repositório Institucional da UFMG - Universidade Federal de Minas Gerais (UFMG) |
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repositorio@ufmg.br |
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15.301603 |