Binding and Structural Properties of DNA Aptamers with VEGF-A-Mimic Activity.

Abstract:

:Vascular endothelial growth factors (VEGFs) are hypoxia-inducible secreted proteins to promote angiogenesis, in which VEGF-A is an important molecule that binds and activates VEGF receptor-1 (VEGFR-1) and VEGFR-2. In this study, two DNA aptamers, Apt01 and Apt02, were successfully isolated by alternating consecutive systematic evolution of ligands by exponential enrichment (SELEX) against VEGFR-1 and -2 using deep sequencing analysis in an early selection round. Their binding affinities for VEGFR-2 were lower than that of VEGFR-1, which is similar to that of VEGF-A. Structural analyses with the measurements of circular dichroism spectra and ultraviolet melting curve showed that Apt01 possessed the stem-loop structure in the molecule, whereas Apt02 formed G-quadruplex structures. In addition, Apt02 accelerated a tube formation of human umbilical vein endothelial cells faster than Apt01, which was affected by difference of binding affinity and nuclease resistance due to G-quadruplex structures. These results demonstrated that Apt02 might have a potential to function as an alternative to VEGF-A.

journal_name

Mol Ther Nucleic Acids

authors

Yoshitomi T,Hayashi M,Oguro T,Kimura K,Wayama F,Furusho H,Yoshimoto K

doi

10.1016/j.omtn.2019.12.034

subject

Has Abstract

pub_date

2020-03-06 00:00:00

pages

1145-1152

issn

2162-2531

pii

S2162-2531(20)30018-4

journal_volume

19

pub_type

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