Medical College of Wisconsin
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DNA Aptamer Assembly as a Vascular Endothelial Growth Factor Receptor Agonist. Nucleic Acid Ther 2015 Oct;25(5):227-34

Date

07/01/2015

Pubmed ID

26125598

Pubmed Central ID

PMC4576944

DOI

10.1089/nat.2014.0519

Scopus ID

2-s2.0-84941888936 (requires institutional sign-in at Scopus site)   68 Citations

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.

Author List

Ramaswamy V, Monsalve A, Sautina L, Segal MS, Dobson J, Allen JB

Author

Josephine Allen PhD, MS Professor in the Pediatrics department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Aptamers, Nucleotide
Cells, Cultured
Drug Evaluation, Preclinical
Human Umbilical Vein Endothelial Cells
Humans
Neovascularization, Physiologic
Nitric Oxide Synthase Type III
Phosphorylation
Protein Processing, Post-Translational
Signal Transduction
Vascular Endothelial Growth Factor Receptor-2