We describe the application of T4 DNA ligase-catalyzed DNA templated oligonucleotide polymerization toward the evolution of a diversely functionalized nucleic acid aptamer for human α-thrombin. Using a 256-membered ANNNN co-monomer library comprising 16 sub-libraries modified with different functional groups, a highly-functionalized aptamer for thrombin was raised with a dissociation constant of 1.6 nM. The aptamer was found to be selective for thrombin, and required the modifications for binding affinity. This study demonstrates the most differentially functionalized nucleic acid aptamer discovered by in vitro selection and should enable the future exploration of functional group dependence during the evolution of nucleic acid polymer activity.

Molecular evolution of densely-functionalized aptamers

255th National Meeting (2018)

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