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.
| Identifer | oai:union.ndltd.org:DRESDEN/oai:qucosa:de:qucosa:89020 |
| Date | 15 January 2024 |
| Creators | Möser, Christin, Lorenz, Jessica S., Sajfutdinow, Martin, Smith, David M. |
| Publisher | MDPI |
| Source Sets | Hochschulschriftenserver (HSSS) der SLUB Dresden |
| Language | English |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, doc-type:article, info:eu-repo/semantics/article, doc-type:Text |
| Rights | info:eu-repo/semantics/openAccess |
| Relation | 3482 |
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