Agonistic aptamer to the insulin receptor leads to biased signaling and functional selectivity through allosteric modulation.
In this study IR-A48 is presented as a biased agonist able to selectively induce the metabolic activity of insulin receptors through allosteric binding. This is the first study to show that aptamer–protein interactions can not only differentially modulate receptor autophosphorylation (IR Y1150), but also induce specific signaling pathways and functional selectivity. Data suggests that aptamers can be a promising tool for developing artificial biased agonists to targeted receptor and that IR-A48 could represent a novel strategy for facilitating insulin action and improving glycemic control in diabetes patients.
The results have been published in the September issue of Nucleic Acids Research.