Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors

Autores
Zanella, Simone; Bocchinfuso, Gianfranco; De Zotti, Marta; Arosio, Daniela; Marino, Franca; Raniolo, Stefano; Pignataro, Luca; Sacco, Giovanni; Palleschi, Antonio; Siano, Alvaro Sebastían; Piarulli, Umberto; Belvisi, Laura; Formaggio, Fernando; Gennari, Cesare; Stella, Lorenzo
Año de publicación
2019
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Tumor angiogenesis, essential for cancer development, is regulated mainly by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), which are overexpressed in cancer cells. Therefore, the VEGF/VEGFR interaction represents a promising pharmaceutical target to fight cancer progression. The VEGF surface interacting with VEGFRs comprises a short α-helix. In this work, helical oligopeptides mimicking the VEGF-C helix were rationally designed based on structural analyses and computational studies. The helical conformation was stabilized by optimizing intramolecular interactions and by introducing helix-inducing C α,α -disubstituted amino acids. The conformational features of the synthetic peptides were characterized by circular dichroism and nuclear magnetic resonance, and their receptor binding properties and antiangiogenic activity were determined. The best hits exhibited antiangiogenic activity in vitro at nanomolar concentrations and were resistant to proteolytic degradation.
Fil: Zanella, Simone. Università degli Studi di Milano; Italia
Fil: Bocchinfuso, Gianfranco. Universita Tor Vergata; Italia
Fil: De Zotti, Marta. Università di Padova; Italia
Fil: Arosio, Daniela. Consiglio Nazionale delle Ricerche; Italia
Fil: Marino, Franca. Università Degli Studi Dell'insubria;
Fil: Raniolo, Stefano. Universita Tor Vergata; Italia
Fil: Pignataro, Luca. Università degli Studi di Milano; Italia
Fil: Sacco, Giovanni. Università degli Studi di Milano; Italia
Fil: Palleschi, Antonio. Universita Tor Vergata; Italia
Fil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral; Argentina
Fil: Piarulli, Umberto. Università Degli Studi Dell'insubria;
Fil: Belvisi, Laura. Università degli Studi di Milano; Italia. Consiglio Nazionale delle Ricerche; Italia
Fil: Formaggio, Fernando. Università di Padova; Italia
Fil: Gennari, Cesare. Università degli Studi di Milano; Italia. Consiglio Nazionale delle Ricerche; Italia
Fil: Stella, Lorenzo. Universita Tor Vergata; Italia
Materia
ANGIOGENESIS
CAlpha
HELICAL FOLDED PEPTIDES
PROTEIN-PROTEIN INTERACTIONS
VEGF-C
Nivel de accesibilidad
acceso abierto
Condiciones de uso
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
Repositorio
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/104696
Acceder
id CONICETDig_90da7ce7cc889b7dd49bfe130c306df9
oai_identifier_str oai:ri.conicet.gov.ar:11336/104696
network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptorsZanella, SimoneBocchinfuso, GianfrancoDe Zotti, MartaArosio, DanielaMarino, FrancaRaniolo, StefanoPignataro, LucaSacco, GiovanniPalleschi, AntonioSiano, Alvaro SebastíanPiarulli, UmbertoBelvisi, LauraFormaggio, FernandoGennari, CesareStella, LorenzoANGIOGENESISCAlphaHELICAL FOLDED PEPTIDESPROTEIN-PROTEIN INTERACTIONSVEGF-Chttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Tumor angiogenesis, essential for cancer development, is regulated mainly by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), which are overexpressed in cancer cells. Therefore, the VEGF/VEGFR interaction represents a promising pharmaceutical target to fight cancer progression. The VEGF surface interacting with VEGFRs comprises a short α-helix. In this work, helical oligopeptides mimicking the VEGF-C helix were rationally designed based on structural analyses and computational studies. The helical conformation was stabilized by optimizing intramolecular interactions and by introducing helix-inducing C α,α -disubstituted amino acids. The conformational features of the synthetic peptides were characterized by circular dichroism and nuclear magnetic resonance, and their receptor binding properties and antiangiogenic activity were determined. The best hits exhibited antiangiogenic activity in vitro at nanomolar concentrations and were resistant to proteolytic degradation.Fil: Zanella, Simone. Università degli Studi di Milano; ItaliaFil: Bocchinfuso, Gianfranco. Universita Tor Vergata; ItaliaFil: De Zotti, Marta. Università di Padova; ItaliaFil: Arosio, Daniela. Consiglio Nazionale delle Ricerche; ItaliaFil: Marino, Franca. Università Degli Studi Dell'insubria; Fil: Raniolo, Stefano. Universita Tor Vergata; ItaliaFil: Pignataro, Luca. Università degli Studi di Milano; ItaliaFil: Sacco, Giovanni. Università degli Studi di Milano; ItaliaFil: Palleschi, Antonio. Universita Tor Vergata; ItaliaFil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral; ArgentinaFil: Piarulli, Umberto. Università Degli Studi Dell'insubria; Fil: Belvisi, Laura. Università degli Studi di Milano; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: Formaggio, Fernando. Università di Padova; ItaliaFil: Gennari, Cesare. Università degli Studi di Milano; Italia. Consiglio Nazionale delle Ricerche; ItaliaFil: Stella, Lorenzo. Universita Tor Vergata; ItaliaFrontiers Media S.A.2019-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/104696Zanella, Simone; Bocchinfuso, Gianfranco; De Zotti, Marta; Arosio, Daniela; Marino, Franca; et al.; Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors; Frontiers Media S.A.; Frontiers in Chemistry; 7; 3-2019; 1-132296-2646CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/doi/10.3389/fchem.2019.00170info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by-nc-sa/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:31:50Zoai:ri.conicet.gov.ar:11336/104696instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 10:31:51.19CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
title Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
spellingShingle Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
Zanella, Simone
ANGIOGENESIS
CAlpha
HELICAL FOLDED PEPTIDES
PROTEIN-PROTEIN INTERACTIONS
VEGF-C
title_short Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
title_full Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
title_fullStr Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
title_full_unstemmed Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
title_sort Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors
dc.creator.none.fl_str_mv Zanella, Simone
Bocchinfuso, Gianfranco
De Zotti, Marta
Arosio, Daniela
Marino, Franca
Raniolo, Stefano
Pignataro, Luca
Sacco, Giovanni
Palleschi, Antonio
Siano, Alvaro Sebastían
Piarulli, Umberto
Belvisi, Laura
Formaggio, Fernando
Gennari, Cesare
Stella, Lorenzo
author Zanella, Simone
author_facet Zanella, Simone
Bocchinfuso, Gianfranco
De Zotti, Marta
Arosio, Daniela
Marino, Franca
Raniolo, Stefano
Pignataro, Luca
Sacco, Giovanni
Palleschi, Antonio
Siano, Alvaro Sebastían
Piarulli, Umberto
Belvisi, Laura
Formaggio, Fernando
Gennari, Cesare
Stella, Lorenzo
author_role author
author2 Bocchinfuso, Gianfranco
De Zotti, Marta
Arosio, Daniela
Marino, Franca
Raniolo, Stefano
Pignataro, Luca
Sacco, Giovanni
Palleschi, Antonio
Siano, Alvaro Sebastían
Piarulli, Umberto
Belvisi, Laura
Formaggio, Fernando
Gennari, Cesare
Stella, Lorenzo
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.subject.none.fl_str_mv ANGIOGENESIS
CAlpha
HELICAL FOLDED PEPTIDES
PROTEIN-PROTEIN INTERACTIONS
VEGF-C
topic ANGIOGENESIS
CAlpha
HELICAL FOLDED PEPTIDES
PROTEIN-PROTEIN INTERACTIONS
VEGF-C
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Tumor angiogenesis, essential for cancer development, is regulated mainly by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), which are overexpressed in cancer cells. Therefore, the VEGF/VEGFR interaction represents a promising pharmaceutical target to fight cancer progression. The VEGF surface interacting with VEGFRs comprises a short α-helix. In this work, helical oligopeptides mimicking the VEGF-C helix were rationally designed based on structural analyses and computational studies. The helical conformation was stabilized by optimizing intramolecular interactions and by introducing helix-inducing C α,α -disubstituted amino acids. The conformational features of the synthetic peptides were characterized by circular dichroism and nuclear magnetic resonance, and their receptor binding properties and antiangiogenic activity were determined. The best hits exhibited antiangiogenic activity in vitro at nanomolar concentrations and were resistant to proteolytic degradation.
Fil: Zanella, Simone. Università degli Studi di Milano; Italia
Fil: Bocchinfuso, Gianfranco. Universita Tor Vergata; Italia
Fil: De Zotti, Marta. Università di Padova; Italia
Fil: Arosio, Daniela. Consiglio Nazionale delle Ricerche; Italia
Fil: Marino, Franca. Università Degli Studi Dell'insubria;
Fil: Raniolo, Stefano. Universita Tor Vergata; Italia
Fil: Pignataro, Luca. Università degli Studi di Milano; Italia
Fil: Sacco, Giovanni. Università degli Studi di Milano; Italia
Fil: Palleschi, Antonio. Universita Tor Vergata; Italia
Fil: Siano, Alvaro Sebastían. Universidad Nacional del Litoral; Argentina
Fil: Piarulli, Umberto. Università Degli Studi Dell'insubria;
Fil: Belvisi, Laura. Università degli Studi di Milano; Italia. Consiglio Nazionale delle Ricerche; Italia
Fil: Formaggio, Fernando. Università di Padova; Italia
Fil: Gennari, Cesare. Università degli Studi di Milano; Italia. Consiglio Nazionale delle Ricerche; Italia
Fil: Stella, Lorenzo. Universita Tor Vergata; Italia
description Tumor angiogenesis, essential for cancer development, is regulated mainly by vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs), which are overexpressed in cancer cells. Therefore, the VEGF/VEGFR interaction represents a promising pharmaceutical target to fight cancer progression. The VEGF surface interacting with VEGFRs comprises a short α-helix. In this work, helical oligopeptides mimicking the VEGF-C helix were rationally designed based on structural analyses and computational studies. The helical conformation was stabilized by optimizing intramolecular interactions and by introducing helix-inducing C α,α -disubstituted amino acids. The conformational features of the synthetic peptides were characterized by circular dichroism and nuclear magnetic resonance, and their receptor binding properties and antiangiogenic activity were determined. The best hits exhibited antiangiogenic activity in vitro at nanomolar concentrations and were resistant to proteolytic degradation.
publishDate 2019
dc.date.none.fl_str_mv 2019-03
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/11336/104696
Zanella, Simone; Bocchinfuso, Gianfranco; De Zotti, Marta; Arosio, Daniela; Marino, Franca; et al.; Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors; Frontiers Media S.A.; Frontiers in Chemistry; 7; 3-2019; 1-13
2296-2646
CONICET Digital
CONICET
url http://hdl.handle.net/11336/104696
identifier_str_mv Zanella, Simone; Bocchinfuso, Gianfranco; De Zotti, Marta; Arosio, Daniela; Marino, Franca; et al.; Rational design of antiangiogenic helical oligopeptides targeting the vascular endothelial growth factor receptors; Frontiers Media S.A.; Frontiers in Chemistry; 7; 3-2019; 1-13
2296-2646
CONICET Digital
CONICET
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/doi/10.3389/fchem.2019.00170
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
eu_rights_str_mv openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-sa/2.5/ar/
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv Frontiers Media S.A.
publisher.none.fl_str_mv Frontiers Media S.A.
dc.source.none.fl_str_mv reponame:CONICET Digital (CONICET)
instname:Consejo Nacional de Investigaciones Científicas y Técnicas
reponame_str CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas
repository.mail.fl_str_mv dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar
_version_ 1844614330673266688
score 13.070432

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