Imino proton exchange rates imply an induced-fit binding mechanism for the VEGF 165-targeting aptamer, Macugen

Abstract

The 2′-fluoro/2′- O-methyl modified RNA aptamer Macugen is a potent inhibitor of the angiogenic regulatory protein, VEGF 165. Macugen binds with high affinity to the heparin-binding domain (HBD) of VEGF 165. Hydrogen exchange rates of the imino protons were measured for free Macugen and Macugen bound to the HBD or full-length VEGF to better understand the mechanism for high affinity binding. The results here show that the internal loop and hairpin loop of Macugen are highly dynamic in the free state and are greatly stabilized and/or protected from solvent upon protein binding.