I Got You: The Strong Bond Between a SOMAmer and Its Protein

What thoughts give you a warm fuzzy feeling? A basket of golden retriever puppies or wriggly mewing kittens? Maybe loved ones or friends? We humans evolved to be social creatures. Without a social network, we could potentially face a lonely existence that wreaks havoc on our mental and physical health (Perissinotto, Stijacic Cenzer, & Covinsky, 2012). We are not alone in our need of social contact: Many creatures from the humble bee to the giants of the sea need connections to thrive.

In a sense, one can imagine that the tiny nucleic acids called “aptamers” are also “evolved” to share a strong connection with a target, such as proteins. The modified aptamers (SOMAmers®), created out of SomaLogic’s proprietary technology, share some of the strongest bonds with their partners that are difficult to break on their own.

In a recent review, researchers at SomaLogic analyzed the binding interaction of SOMAmers with their targets and compared them to the ones shared between unmodified aptamers and their targets (Gelinas, Davies, & Janjic, 2016). The analysis revealed that the SOMAmer’s unique modifications are critical to the strength of the binding event. This type of binding tends to be stronger than interactions between aptamer and protein, which involve base stacking (an arrangement of nucleic acid bases and amino acids that resembles a stack of pancakes), hydrogen bonding, and electrostatic interactions (positively charged molecules binding to negatively charged molecules). The strong interaction shared between a SOMAmer and its target is more reminiscent of the interaction between antibodies and their proteins than of DNA-protein interactions.

Aside from analyzing the binding interactions, the researchers also compared the structures of both aptamers and SOMAmers. In their analysis, they observed that both aptamers and SOMAmers shared some structural elements that are abundant in the nucleic acid structure field. With their modifications, however, SOMAmers go on to adopt many new and novel structures.  It is increasingly clear that SOMAmer modifications provide the glue that can both hold the SOMAmer together and drive the strong bond with its specific target protein partner.

References

Gelinas, A. D., Davies, D. R., & Janjic, N. (2016). Embracing proteins: structural themes in aptamer-protein complexes. Curr Opin Struct Biol, 36, 122-132. doi:10.1016/j.sbi.2016.01.009

Perissinotto, C. M., Stijacic Cenzer, I., & Covinsky, K. E. (2012). Loneliness in older persons: a predictor of functional decline and death. Arch Intern Med, 172(14), 1078-1083. doi:10.1001/archinternmed.2012.1993