TY  - JOUR
A1  - Möser, Christin
A1  - Lorenz, Jessica S.
A1  - Sajfutdinow, Martin
A1  - Smith, David M.
T1  - Pinpointed Stimulation of EphA2 Receptors via DNA-Templated Oligovalence
JF  - International journal of molecular sciences
N2  - DNA nanostructures enable the attachment of functional molecules to nearly any unique location on their underlying structure. Due to their single-base-pair structural resolution, several ligands can be spatially arranged and closely controlled according to the geometry of their desired target, resulting in optimized binding and/or signaling interactions. Here, the efficacy of SWL, an ephrin-mimicking peptide that binds specifically to EphrinA2 (EphA2) receptors, increased by presenting up to three of these peptides on small DNA nanostructures in an oligovalent manner. Ephrin signaling pathways play crucial roles in tumor development and progression. Moreover, Eph receptors are potential targets in cancer diagnosis and treatment. Here, the quantitative impact of SWL valency on binding, phosphorylation (key player for activation) and phenotype regulation in EphA2-expressing prostate cancer cells was demonstrated. EphA2 phosphorylation was significantly increased by DNA trimers carrying three SWL peptides compared to monovalent SWL. In comparison to one of EphA2’s natural ligands ephrin-A1, which is known to bind promiscuously to multiple receptors, pinpointed targeting of EphA2 by oligovalent DNA-SWL constructs showed enhanced cell retraction. Overall, we show that DNA scaffolds can increase the potency of weak signaling peptides through oligovalent presentation and serve as potential tools for examination of complex signaling pathways.
KW  - DNA nanostructure
KW  - ephrin
KW  - EphA2
KW  - SWL
KW  - PC-3 cells
KW  - multivalence
Y1  - 2018
U6  - https://doi.org/10.3390/ijms19113482
SN  - 1422-0067
VL  - 19
IS  - 11
PB  - MDPI
CY  - Basel
ER  -