Abstract
AMPA receptor antagonists are drug candidates for potential treatment of a number of CNS diseases that involve excessive receptor activation. To date, small-molecule compounds are the dominating drug candidates in the field. However, lower potency, cross activity and poor water solubility are generally associated with these compounds. Here we show the potential of RNA-based antagonists or RNA aptamers as drug candidates and some strategies to discover these aptamers from a random sequence library (∼1014 sequences). As an alternative to small molecule compounds, our aptamers exhibit higher potency and selectivity toward AMPA receptors. Because aptamers are RNA molecules, they are naturally water soluble. We also discuss the major challenges of translating RNA aptamers as lead molecules into drugs/treatment options.
Financial & competing interests disclosure
The Project was sponsored by the US Department of Defense (W81XWH-04-1-0106) and NIH (R01NS060812 and R21NS106392). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
No writing assistance was utilized in the production of this manuscript.