Recent advances in the creation of DNA aptamers with non-natural bases, via the systematic evolution of ligands by exponential enrichment (SELEX), have allowed DNA oligomers to move beyond canonical protein-nucleic acid interactions and transition to applications in drug discovery. The Slow Off-rate aptamers (SOMAmers©) generated by such in vitro evolution technologies are not constrained by conventional periodic DNA architectures and as such can attain the structural diversity previously only associated with protein and RNA polymers. The ability of a DNA aptamer to fold into a unique conformation which is both structurally stable and able to bind targets specifically, opens the way for a number of potential drug discovery uses. Presented is a three dimensional analysis of the structures and properties of such SOMAmers©, their contacts with target proteins and an atomic level comparison of the equivalent interactions with protein counterparts. Further, the possibilities for unique interaction modalities of DNA aptamers with target molecules that would not be possible with protein scaffolds will be demonstrated.

Unnatural DNA aptamers and the potential to generate unique macromolecular targeting modalities

251st National Meeting (2016)

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