Angiogenesis is a biological process finely tuned by a plethora of pro- and anti-angiogenic molecules, among which vascular endothelial growth factors (VEGFs). Their biological activity is expressed through the interaction with three cognate receptor tyrosine kinases, VEGFR1, 2, and 3. VEGFR2 is the primary regulator of angiogenesis. Ligand-induced VEGFR2 dimerization and activation depend on direct ligand binding to extracellular domains 2 and 3 of receptor and in the establishment of interactions between proximal membrane domains. VEGFR2 domain 7 has been shown to play a crucial role in receptor dimerization and regulation, therefore, representing a convenient target for the allosteric modulation of VEGFR2 activity. The ability to prepare a functional VEGFR2D7 domain represents the starting point to the development of novel VEGFR2 binders acting as allosteric inhibitors of receptor activity. Here, we describe a robust and efficient procedure for the preparation in E. coli of the VEGFR2 domain 7. The protein was obtained with a good yield and was properly folded. It was investigated in a biochemical and structural study, providing information on its conformational arrangement and in solution properties.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1007/s12033-019-00211-4 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
In Silico Analysis of Triamterene as a Potential Dual Inhibitor of VEGFR-2 and c-Met Receptors.
J Xenobiot
December 2024
Cancer Biology and Therapy Laboratory, School of Applied and Health Sciences, London South Bank University, London SE1 0AA, UK.
The vascular endothelial growth factor receptor 2 (VEGFR2) and the hepatocyte growth factor receptor (C-Met) are critical receptors for signaling pathways controlling crucial cellular processes such as cell growth, angiogenesis and tissue regeneration. However, dysregulation of these proteins has been reported in different diseases, particularly cancer, where these proteins promote tumour growth, invasiveness, metastasis and resistance to conventional therapies. The identification of dual inhibitors targeting both VEGFR-2 and c-Met has emerged as a strategic therapeutic approach to overcome the limitations and resistance mechanisms associated with single-target therapies in clinical settings.
View Article and Find Full Text PDFDCBLD1 Modulates Angiogenesis by Regulation of the VEGFR-2 Endocytosis in Endothelial Cells.
Arterioscler Thromb Vasc Biol
February 2025
Department of Biochemistry and Molecular Biology, School of Basic Medicine, Hebei Medical University, Shijiazhuang, Hebei Province, China (Q.F., C.Y., L.G., X.L., Y.L., C.L., W.Z., Y.Z., W.Y., Y.M., R.W., L.L., Y.P., H.W., M.H., L.N.).
Background: Unwanted angiogenesis is involved in the progression of various malignant tumors and cardiovascular diseases, and the factors that regulate angiogenesis are potential therapeutic targets. We tested the hypothesis that DCBLD1 (discoidin, CUB, and LCCL domain-containing protein 1) is a coreceptor of VEGFR-2 (vascular endothelial growth factor receptor-2) and modulates angiogenesis in endothelial cells.
Methods: A carotid artery ligation model and retinal angiogenesis assay were used to study angiogenesis using globe knockout or endothelial cell-specific conditional knockout mice in vivo.
Design and Discovery of New Dual Carbonic Anhydrase IX and VEGFR-2 Inhibitors Based on the Benzenesulfonamide-Bearing 4-Thiazolidinones/2,4-Thiazolidinediones Scaffold.
Drug Dev Res
December 2024
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hacettepe University, Ankara, Turkey.
Dual-targeting drug design has become a popular approach in investigating and developing potent anticancer agents. In this regard, carbonic anhydrase (CAIX) and vascular endothelial growth factor receptor (VEGFR-2) are emerging as highly effective targets in the battle against cancer. In the present study, two series of 4-thiazolidinones/2,4-thiazolidinediones carrying 2-methylbenzenesulfonamide derivatives were designed and synthesized as potential dual CAIX/VEGFR-2 inhibitors.
View Article and Find Full Text PDFPhosphazene Tripeptide Conjugates: Design, Synthesis, In Vitro Cytotoxicity and Genotoxicity, Molecular Interactions in Binding Pockets on Human Breast and Colon Cancer Cell Lines.
ChemMedChem
October 2024
Department of Chemistry, Faculty of Science, Marmara University, Istanbul, Türkiye.
The biological activity of both cyclophosphazenes and peptides makes these compounds important for new studies in medicinal chemistry. For this purpose, five different phosphazene-peptide conjugates synthesized from dichlorocyclotriphosphazene and tyrosine-containing tripeptides. The synthesized compounds were evaluated for their in vitro cytotoxic activities against human breast (MCF-7) and colon (Caco-2) cancer cell lines using MTT assay.
View Article and Find Full Text PDFRole of β-adrenergic signaling and the NLRP3 inflammasome in chronic intermittent hypoxia-induced murine lung cancer progression.
Respir Res
September 2024
Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Xinxiang Medical University, 88 Jiankang Road, Weihui, Henan, 453100, Henan, China.
Background: Obstructive sleep apnea (OSA), characterized by chronic intermittent hypoxia (CIH), is a prevalent condition that has been associated with various forms of cancer. Although some clinical studies suggest a potential link between OSA and lung cancer, this association remains uncertain, and the underlying mechanisms are not fully understood. This study investigated the role of the catecholamine-β-adrenergic receptor (βAR) and the NLRP3 inflammasome in mediating the effects of CIH on lung cancer progression in mice.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!