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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...

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Autores principales: Balsera, Beatriz, Bonache, M. Ángeles, Reille-Seroussi, Marie, Gagey-Eilstein, Nathalie, Vidal, Michel, González-Muñiz, Rosario, Pérez de Vega, María Jesús
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
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.
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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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