This invention relates to methods of preparing nucleic acid aptamers having selectivity for target substrates. In particular the present invention provides for a method of identifying a ligand binding domain (LBD) in an aptamer by providing a first incubation solution by incubating an aptamer with a target substrate in a first appropriate solvent; and adding an exonuclease enzyme to the first incubation solution to form a second incubation solution in a second appropriate solvent and incubating the second incubation solution, wherein the exonuclease enzyme digests aptamer and provides an aptamer comprising the ligand binding domain.