In an article published online in Nature Communications, scientists from SomaLogic and Yale University report that they have successfully generated a novel Slow Off-rate Modified Aptamer (SOMAmer) molecule that binds tightly to interleukin 1 alpha (IL-1α), an essential inflammatory protein implicated in cancer and other diseases. The SOMAmer (called SL1067) shows high specificity for IL-1α and can block its activity. SL1067 could therefore be a useful tool for elucidating IL-1α’s role in producing inflammation and regulating the immune system.

IL-1α/SL1067 structure with IL-1α in green. SL1067 is in cyan with naphthyl-modified residues in orange.

The researchers determined the three-dimensional structure of SL1067 bound to IL-1α, providing the first high-resolution structure of this essential protein. This is also the first crystal structure of a SOMAmer that contains bases modified with naphthyl groups, five of which are involved in IL-1α binding. The naphthyl modifications allow SL1067 to adopt a very compact structure with unusual three-dimensional shapes that have never been seen before. Since SL1067 is small (only 22 nucleotides in length), stable and easily synthesized, it serves as an excellent starting point for development of novel therapeutic molecules that target IL-1α.

 

Ren, X et al. (2017) “Structural basis for IL-1α recognition by a modified DNA aptamer that specifically inhibits IL-1α signaling” Nat Commun, epub ahead of print.
https://www.nature.com/articles/s41467-017-00864-2