Intramers and Aptamers: Applications in Protein‐Function Analyses and Potential for Drug Screening

An RNA molecule that specifically inhibits G-protein-coupled receptor kinase 2 in vitro

“…The aptamer possesses high specificity toward GRK2 as compared to other kinases and thus represents a promising starting point for the functional interference and analysis of endogenous GRK2 function inside cells and living organisms. For example the aptamer can be either directly transfected into cells or expressed from plasmids that encode the aptamer sequence under certain promoter elements (Mayer et al 2001;Theis et al 2004;Famulok and Mayer 2005). Recent studies demonstrated that aptamers can be converted into small molecule inhibitors using so-called aptamer-displacement assays (Hafner et al 2006).…”

“…Furthermore, aptamers have been shown to be potent and specific inhibitors of several protein classes both in the extracellular and intracellular environment (Famulok and Mayer 2005). Once an inhibitory aptamer has been identified and validated, the chemical information stored in the aptamer might be converted into a small druglike molecule with the inherited properties of the parent aptamer (Hartig et al 2002;Hafner et al 2006).…”

“…Once an inhibitory aptamer has been identified and validated, the chemical information stored in the aptamer might be converted into a small druglike molecule with the inherited properties of the parent aptamer (Hartig et al 2002;Hafner et al 2006). By this means the versatility of in vitro selection can be combined with the ease of applying small molecules to cells or living organisms, which can be applied to investigate protein function and further serve as leads for therapeutic drug development (Burgstaller et al 2002a,b;Famulok and Mayer 2005). We applied in vitro selection to identify a highly specific RNA aptamer that binds to GRK2 and inhibits its kinase function.…”

Anti-miRNA oligonucleotides (AMOs): ammunition to target miRNAs implicated in human disease?

“…RNA ligands that are naturally selected to bind protein targets specifically are referred to as aptamers. 47 In this case, inhibition is likely due to direct binding of Dicer as well as competition for the Exportin 5 nuclear export factor.…”

Molecular tools for cell and systems biology

“…Aptamers are short single-stranded oligonucleotides that fold into a distinct three-dimensional structure. They bind their targets with high affinity by complementary shape interactions (Famulok and Mayer, 2005;Famulok et al, 2000). The high specificity is generated by using combinatorial sequence libraries and a method called SELEX (systematic evolution of ligands by exponential enrichment), an in vitro selection process.…”