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Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF(13-25) 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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150346/ https://www.ncbi.nlm.nih.gov/pubmed/29143774 http://dx.doi.org/10.3390/molecules22111846 |
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author | Balsera, Beatriz Bonache, M. Ángeles Reille-Seroussi, Marie Gagey-Eilstein, Nathalie Vidal, Michel González-Muñiz, Rosario Pérez de Vega, María Jesús |
author_facet | Balsera, Beatriz Bonache, M. Ángeles Reille-Seroussi, Marie Gagey-Eilstein, Nathalie Vidal, Michel González-Muñiz, Rosario Pérez de Vega, María Jesús |
author_sort | Balsera, Beatriz |
collection | PubMed |
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-SSEEX(5)ARNX(9)AAX(12)N-NH(2)), 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 IC(50) 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. |
format | Online Article Text |
id | pubmed-6150346 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-61503462018-11-13 Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF(13-25) Fragment Balsera, Beatriz Bonache, M. Ángeles Reille-Seroussi, Marie Gagey-Eilstein, Nathalie Vidal, Michel González-Muñiz, Rosario Pérez de Vega, María Jesús Molecules Article 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-SSEEX(5)ARNX(9)AAX(12)N-NH(2)), 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 IC(50) 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. MDPI 2017-10-28 /pmc/articles/PMC6150346/ /pubmed/29143774 http://dx.doi.org/10.3390/molecules22111846 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Balsera, Beatriz Bonache, M. Ángeles Reille-Seroussi, Marie Gagey-Eilstein, Nathalie Vidal, Michel González-Muñiz, Rosario Pérez de Vega, María Jesús Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF(13-25) Fragment |
title | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF(13-25) Fragment |
title_full | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF(13-25) Fragment |
title_fullStr | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF(13-25) Fragment |
title_full_unstemmed | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF(13-25) Fragment |
title_short | Disrupting VEGF–VEGFR1 Interaction: De Novo Designed Linear Helical Peptides to Mimic the VEGF(13-25) Fragment |
title_sort | disrupting vegf–vegfr1 interaction: de novo designed linear helical peptides to mimic the vegf(13-25) fragment |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6150346/ https://www.ncbi.nlm.nih.gov/pubmed/29143774 http://dx.doi.org/10.3390/molecules22111846 |
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