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Pinpointed Stimulation of EphA2 Receptors via DNA-Templated Oligovalence.

A new interesting article has been published in Int J Mol Sci. 2018 Nov 6;19(11). pii: E3482. doi: 10.3390/ijms19113482. and titled:

Pinpointed Stimulation of EphA2 Receptors via DNA-Templated Oligovalence.

Authors of this article are:

Möser C, Lorenz JS, Sajfutdinow M, Smith DM.

A summary of the article is shown below:

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.

Check out the article’s website on Pubmed for more information:

This article is a good source of information and a good way to become familiar with topics such as:

DNA nanostructure;EphA2;PC-3 cells;SWL;ephrin;multivalence


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