Our cubane phosphoramidite enables the incorporation of a compact, three-dimensional hydrophobic cubane moiety into oligonucleotides, expanding the chemical diversity of nucleic acids and enabling distinct modes of interaction with biological targets. Incorporation of cubane into aptamers has led to so-called cubamers, which have demonstrated new protein recognition properties. Notably, cubamers have been shown to distinguish the malaria biomarker Plasmodium vivax lactate dehydrogenase (PvLDH) from the closely related Plasmodium falciparum lactate dehydrogenase (PfLDH), despite their high sequence homology. The cubane modification has also been successfully incorporated into siRNAs at different positions while retaining potent gene-silencing activity, highlighting its potential as a novel structural modification for RNA research. These studies demonstrate the versatility of cubane phosphoramidites for next-generation aptamers, biomarker detection, diagnostics, and RNA therapeutics research.

Literature: Cheung, Y.-W. et al. Evolution of abiotic cubane chemistries in a nucleic acid aptamer allows selective recognition of a malaria biomarker. Proceedings of the National Academy of Sciences 117, 16790–16795 (2020). DOI: 10.1073/pnas.2003267117.

Hammill, M. L. et al. Building siRNAs with Cubes: Synthesis and Evaluation of Cubane-Modified siRNAs. ChemBioChem 22, 2981–2985 (2021). DOI: 10.1002/cbic.202100334.