Front Cover: Interrogating Aptamer Chemical Space Through Modified Nucleotide Substitution Facilitated by Enzymatic DNA Synthesis (ChemBioChem 1/2024)

Chemically modified aptamers are typically obtained through SELEX with unnatural nucleotides. If binding affinity or specificity falls short, re‐selection or post‐SELEX methods that are often time‐consuming or synthetically challenging become necessary. To address these issues, we present a chemoenzymatic method for further aptamer modification. Here, we substituted the cubane‐side chains of a previously identified aptamer with bioisosteres and modified cubane moieties using polymerase‐mediated synthesis. This method offers a practical way to streamline post‐SELEX optimization efforts. More information can be found in the Research Article by M. Hollenstein et al.