Evolution of Functionally Enhanced α-<scp>l</scp>-Threofuranosyl Nucleic Acid Aptamers
Cailen M. McCloskey, Qingfeng Li, Eric J. Yik, Nicholas Chim, Arlene K. Ngor, Esau Medina, Ivan Grubišić, Lance Co Ting Keh, Ryan Poplin, John C. Chaput
Abstract
selection and next-generation sequencing using uracil nucleotides that are uniformly equipped with aromatic side chains commonly found in the paratope of antibody-antigen crystal structures. Kinetic measurements reveal that the side chain modifications are critical for generating threomers with slow off-rate binding kinetics. These findings expand the chemical space of evolvable non-natural genetic systems to include functional groups that enhance protein target binding by mimicking the structural properties of traditional antibodies.
Topics & Concepts
AptamerNucleic acidComputational biologySystematic evolution of ligands by exponential enrichmentChemistryDirected evolutionBiologyBiochemistryCell biologyMolecular biologyRNAGeneMutantAdvanced biosensing and bioanalysis techniquesDNA and Nucleic Acid ChemistryRNA Interference and Gene Delivery