A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics

The vascular endothelial growth factor (VEGF) family of cytokines plays a key role in vasculogenesis, angiogenesis, and lymphangiogenesis. VEGF-A is the main member of this family, alongside placental growth factor (PlGF), VEGF-B/C/D in mammals, and VEGF-E/F in other organisms. To study the activiti...

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Autores principales:	Xiaoqing Ye, Jean-François Gaucher, Michel Vidal, Sylvain Broussy
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	vascular endothelial growth factors ligands structures pharmacological inhibition macromolecules peptides Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/5834be487b454718a4c6412d723aef0f
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spelling	oai:doaj.org-article:5834be487b454718a4c6412d723aef0f2021-11-25T18:27:02ZA Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics10.3390/molecules262267591420-3049https://doaj.org/article/5834be487b454718a4c6412d723aef0f2021-11-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/22/6759https://doaj.org/toc/1420-3049The vascular endothelial growth factor (VEGF) family of cytokines plays a key role in vasculogenesis, angiogenesis, and lymphangiogenesis. VEGF-A is the main member of this family, alongside placental growth factor (PlGF), VEGF-B/C/D in mammals, and VEGF-E/F in other organisms. To study the activities of these growth factors under physiological and pathological conditions, resulting in therapeutic applications in cancer and age-related macular degeneration, blocking ligands have been developed. These have mostly been large biomolecules like antibodies. Ligands with high affinities, at least in the nanomolar range, and accurate structural data from X-ray crystallography and NMR spectroscopy have been described. They constitute the main focus of this overview, which evidences similarities and differences in their binding modes. For VEGF-A ligands, and to a limited extent also for PlGF, a transition is now observed towards developing smaller ligands like nanobodies and peptides. These include unnatural amino acids and chemical modifications for designed and improved properties, such as serum stability and greater affinity. However, this review also highlights the scarcity of such small molecular entities and the striking lack of small organic molecule ligands. It also shows the gap between the rather large array of ligands targeting VEGF-A and the general absence of ligands binding other VEGF members, besides some antibodies. Future developments in these directions are expected in the upcoming years, and the study of these growth factors and their promising therapeutic applications will be welcomed.Xiaoqing YeJean-François GaucherMichel VidalSylvain BroussyMDPI AGarticlevascular endothelial growth factorsligandsstructurespharmacological inhibitionmacromoleculespeptidesOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6759, p 6759 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	vascular endothelial growth factors ligands structures pharmacological inhibition macromolecules peptides Organic chemistry QD241-441
spellingShingle	vascular endothelial growth factors ligands structures pharmacological inhibition macromolecules peptides Organic chemistry QD241-441 Xiaoqing Ye Jean-François Gaucher Michel Vidal Sylvain Broussy A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics
description	The vascular endothelial growth factor (VEGF) family of cytokines plays a key role in vasculogenesis, angiogenesis, and lymphangiogenesis. VEGF-A is the main member of this family, alongside placental growth factor (PlGF), VEGF-B/C/D in mammals, and VEGF-E/F in other organisms. To study the activities of these growth factors under physiological and pathological conditions, resulting in therapeutic applications in cancer and age-related macular degeneration, blocking ligands have been developed. These have mostly been large biomolecules like antibodies. Ligands with high affinities, at least in the nanomolar range, and accurate structural data from X-ray crystallography and NMR spectroscopy have been described. They constitute the main focus of this overview, which evidences similarities and differences in their binding modes. For VEGF-A ligands, and to a limited extent also for PlGF, a transition is now observed towards developing smaller ligands like nanobodies and peptides. These include unnatural amino acids and chemical modifications for designed and improved properties, such as serum stability and greater affinity. However, this review also highlights the scarcity of such small molecular entities and the striking lack of small organic molecule ligands. It also shows the gap between the rather large array of ligands targeting VEGF-A and the general absence of ligands binding other VEGF members, besides some antibodies. Future developments in these directions are expected in the upcoming years, and the study of these growth factors and their promising therapeutic applications will be welcomed.
format	article
author	Xiaoqing Ye Jean-François Gaucher Michel Vidal Sylvain Broussy
author_facet	Xiaoqing Ye Jean-François Gaucher Michel Vidal Sylvain Broussy
author_sort	Xiaoqing Ye
title	A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics
title_short	A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics
title_full	A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics
title_fullStr	A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics
title_full_unstemmed	A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics
title_sort	structural overview of vascular endothelial growth factors pharmacological ligands: from macromolecules to designed peptidomimetics
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/5834be487b454718a4c6412d723aef0f
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A Structural Overview of Vascular Endothelial Growth Factors Pharmacological Ligands: From Macromolecules to Designed Peptidomimetics

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