title: DNA Aptamer Assembly as a Vascular Endothelial Growth Factor Receptor Agonist.
abstract: Controlling receptor-mediated processes in cells is paramount in many research areas. The activity of small molecules and growth factors is difficult to control and can lead to off-target effects through the activation of nonspecific receptors as well as binding affinity to nonspecific cell types. In this study, we report the development of a molecular trigger in the form of a divalent nucleic acid aptamer assembly toward vascular endothelial growth factor receptor-2 (VEGFR2). The assembly binds to VEGFR2 and functions as a receptor agonist with targeted receptor binding, promoting receptor phosphorylation, activation of the downstream Akt pathway, upregulation of endothelial nitric oxide synthase, and endothelial cell capillary tube formation. The agonist action we report makes this aptamer construct a promising strategy to control VEGFR2-mediated cell signaling.
authors.affiliation: 1 Department of Materials Science and Engineering, University of Florida , Gainesville, Florida.
authors.forename: Vidhya
authors.initials: V
authors.lastname: Ramaswamy
authors.affiliation: 1 Department of Materials Science and Engineering, University of Florida , Gainesville, Florida.
authors.forename: Adam
authors.initials: A
authors.lastname: Monsalve
authors.affiliation: 2 Division of Nephrology, College of Medicine, University of Florida , Gainesville, Florida.
authors.forename: Larysa
authors.initials: L
authors.lastname: Sautina
authors.affiliation: 2 Division of Nephrology, College of Medicine, University of Florida , Gainesville, Florida.|3 North Florida/South Georgia Veterans Health System , Gainesville, Florida.
authors.forename: Mark S
authors.initials: MS
authors.lastname: Segal
authors.affiliation: 1 Department of Materials Science and Engineering, University of Florida , Gainesville, Florida.|4 J. Crayton Pruitt Family Department of Biomedical Engineering, University of Florida , Gainesville, Florida.|5 Institute of Cellular Engineering and Regenerative Medicine, University of Florida , Gainesville, Florida.
authors.forename: Jon
authors.initials: J
authors.lastname: Dobson
authors.affiliation: 1 Department of Materials Science and Engineering, University of Florida , Gainesville, Florida.|5 Institute of Cellular Engineering and Regenerative Medicine, University of Florida , Gainesville, Florida.
authors.forename: Josephine B
authors.initials: JB
authors.lastname: Allen
mesh_terms: D052157:Aptamers, Nucleotide / Q000494:pharmacology*; D002478:Cells, Cultured; D004353:Drug Evaluation, Preclinical; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D018919:Neovascularization, Physiologic / Q000187:drug effects; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D015398:Signal Transduction; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000819:agonists* / Q000378:metabolism
chemical_list: D052157:Aptamers, Nucleotide; C496314:NOS3 protein, human; D052250:Nitric Oxide Synthase Type III; C000588866:KDR protein, human; D040301:Vascular Endothelial Growth Factor Receptor-2