Implications of Natural 3′–5′– Linkages in the Loop Region of Isomeric 2′–5′–Linked Thrombin–Binding Aptamer

The backbone modification of the thrombin‐binding aptamer (TBA) in the TT and TGT loop regions by isomeric 2′–5′–linkages was found to impose additive destabilizing effects on the thermal stability of the G‐quadruplex structure. In contrast, the thermal stability of isomeric 2′–5′–linked TBA, i. e., isoTBA, was significantly improved by isomeric 3′–5′–phosphodiester linkages. The isoTBA, when modified with 3′–5′–linkages in both lateral TT loops (isoTBA202), exhibited higher thermal stability and enzymatic stability in comparison to other oligomers in the present study, and TBA202 showed higher antithrombin activity than other loop‐modified TBA oligomers.