Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment
The interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis and cancer, which moved us to search for peptide derivatives able to block this protein–protein interaction. In a previous work we had described a collection of line...
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MDPI AG
2017-10-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/22/11/1846 |
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| author | Beatriz Balsera M. Ángeles Bonache Marie Reille-Seroussi Nathalie Gagey-Eilstein Michel Vidal Rosario González-Muñiz María Jesús Pérez de Vega |
| author_facet | Beatriz Balsera M. Ángeles Bonache Marie Reille-Seroussi Nathalie Gagey-Eilstein Michel Vidal Rosario González-Muñiz María Jesús Pérez de Vega |
| author_sort | Beatriz Balsera |
| collection | DOAJ |
| description | The interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis and cancer, which moved us to search for peptide derivatives able to block this protein–protein interaction. In a previous work we had described a collection of linear 13-mer peptides specially designed to adopt helical conformations (Ac-SSEEX5ARNX9AAX12N-NH2), as well as the evaluation of seven library components for the inhibition of the interaction of VEGF with its Receptor 1 (VEGFR1). This study led to the discovery of some new, quite potent inhibitors of this protein–protein system. The results we found prompted us to extend the study to other peptides of the library. We describe here the evaluation of a new selection of peptides from the initial library that allow us to identify new VEGF-VEGFR1 inhibitors. Among them, the peptide sequence containing F, W, and I residues at the 5, 9, and 12 positions, show a very significant nanomolar IC50 value, competing with VEGF for its receptor 1, VEGFR1 (Flt-1), which could represent a new tool within the therapeutic arsenal for cancer detection and therapy. |
| first_indexed | 2024-12-23T21:11:11Z |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-23T21:11:11Z |
| publishDate | 2017-10-01 |
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| record_format | Article |
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| spelling | doaj.art-b5119049a937466c95286b63caa9caaf2022-12-21T17:31:03ZengMDPI AGMolecules1420-30492017-10-012211184610.3390/molecules22111846molecules22111846Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 FragmentBeatriz Balsera0M. Ángeles Bonache1Marie Reille-Seroussi2Nathalie Gagey-Eilstein3Michel Vidal4Rosario González-Muñiz5María Jesús Pérez de Vega6Instituto de Química-Médica (IQM-CSIC), Juan de la Cierva 3, Madrid 28006, SpainInstituto de Química-Médica (IQM-CSIC), Juan de la Cierva 3, Madrid 28006, SpainUMR 8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, 4 avenue de l’Observatoire, Paris 75006, FranceUMR 8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, 4 avenue de l’Observatoire, Paris 75006, FranceUMR 8638 CNRS, UFR de Pharmacie, Université Paris Descartes, PRES Sorbonne Paris Cité, 4 avenue de l’Observatoire, Paris 75006, FranceInstituto de Química-Médica (IQM-CSIC), Juan de la Cierva 3, Madrid 28006, SpainInstituto de Química-Médica (IQM-CSIC), Juan de la Cierva 3, Madrid 28006, SpainThe interaction between vascular endothelial growth factor (VEGF) and its receptors (VEGFR) has important implications in angiogenesis and cancer, which moved us to search for peptide derivatives able to block this protein–protein interaction. In a previous work we had described a collection of linear 13-mer peptides specially designed to adopt helical conformations (Ac-SSEEX5ARNX9AAX12N-NH2), as well as the evaluation of seven library components for the inhibition of the interaction of VEGF with its Receptor 1 (VEGFR1). This study led to the discovery of some new, quite potent inhibitors of this protein–protein system. The results we found prompted us to extend the study to other peptides of the library. We describe here the evaluation of a new selection of peptides from the initial library that allow us to identify new VEGF-VEGFR1 inhibitors. Among them, the peptide sequence containing F, W, and I residues at the 5, 9, and 12 positions, show a very significant nanomolar IC50 value, competing with VEGF for its receptor 1, VEGFR1 (Flt-1), which could represent a new tool within the therapeutic arsenal for cancer detection and therapy.https://www.mdpi.com/1420-3049/22/11/1846peptidesα-helixprotein–protein interactionsVEGF-VEGFR1angiogenesis |
| spellingShingle | Beatriz Balsera M. Ángeles Bonache Marie Reille-Seroussi Nathalie Gagey-Eilstein Michel Vidal Rosario González-Muñiz María Jesús Pérez de Vega Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment Molecules peptides α-helix protein–protein interactions VEGF-VEGFR1 angiogenesis |
| title | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment |
| title_full | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment |
| title_fullStr | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment |
| title_full_unstemmed | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment |
| title_short | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF13-25 Fragment |
| title_sort | disrupting vegf vegfr1 interaction de novo designed linear helical peptides to mimic the vegf13 25 fragment |
| topic | peptides α-helix protein–protein interactions VEGF-VEGFR1 angiogenesis |
| url | https://www.mdpi.com/1420-3049/22/11/1846 |
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