Click Capture SELEX for the Identification of Click‐Modified Aptamers Targeting Small Molecules in Solution

Capture SELEX is an in vitro selection method used to identify aptamers that bind small molecules in solution. The interaction of aptamers with their targets is primarily determined by supramolecular interactions, which are constrained by the chemical diversity of the canonical nucleobases. To overcome this limitation, the interaction properties of nucleic acid libraries can be expanded using nucleobase modifications. We developed click capture SELEX for the purpose of enriching chemically modified aptamers, also referred to as clickmers, which bind to small molecules. In this study, an indole-modified DNA library was utilized to identify clickmers that bind specifically to kanamycin A. The click capture SELEX approach was employed to identify clickmers that bind small molecules in solution, thereby overcoming common limitations associated with using immobilized small target molecules in SELEX. The method described herein is generally adaptable to various small molecules.