To assemble these compounds to bind to the two sites in pre-miR-377, peptoid based linkers were synthesized with varying distances between an amine and an azide handle to couple compounds 1A and 2A via an amide coupling and copper-catalyzed click reaction, respectively. The compound series was studied for binding to a mimic of pre-miR-377 and showed that the dimer with four N-n-propyl-glycine spacers bound with the highest affinity (Kd of 5±1 nM) with no measured binding to a base paired mutant RNA (Fig. ). Thus, this compound is referred to as Targapre-miR-377 (TGP-377). In vitro, TGP-377 inhibited Dicer processing of pre-miR-377 with an IC50 of ~500 nM, a 10fold improvement over TGP-377/421. Furthermore, mutation of binding sites for both compounds to base pairs ablated TGP-377's inhibitory effect, demonstrating binding site dependence for activity (Fig. ). TGP-377 is a potent and selective inhibitor of pre-miR-377 processing and stimulates VEGFA production in HUVECs. Delivery of TGP-377 to HUVECs decreased mature miR-377 levels 10-fold more potently than TGP-377/421 (Fig. ). As expected based on its mode of action, TGP-377 increased pre-miR-377 levels by 1.6-fold when HUVECs were treated with 500 nM of compound (Fig. ).