ANCHORED LIGAND AGENTS

摘要

The invention provides novel therapeutic agents comprising ligand molecules such as aptamers linked to a molecular anchor (MA). In the absence of a MA, ligands rapidly diffuse into bulk solution after dissociation from a target molecule. With a MA tightly bound to the target molecule, anchored ligand molecules of the invention remain in close proximity to the active site on the target molecule, even after dissociating from the target, permitting rapid re- binding of ligand to its target. Reversibility of binding to the active site can be effectively and rapidly achieved using antidotes based on the complementary DNA sequences. A preferred embodiment in accordance with the invention is a highly efficient anticoagulant agent that demonstrates binding efficiency to thrombin that is increased many fold relative to a corresponding unanchored aptamer-based ligand.