Protein Labeling and Crosslinking by Covalent Aptamers

We developed a new approach to selectively modify native proteins in their biological environment using electrophilic covalent aptamers. These aptamers are generated through introduction of a proximity-driven electrophile at specific nucleotide sites. Using thrombin as a proof-of-concept, we demonstrate that covalent aptamers can selectively transfer a variety of functional handles and/or irreversibly crosslink to the target protein. This approach offers broad programmability and high target specificity. Furthermore, it addresses issues common to aptamers such as instability towards endogenous nucleases and residence times during target engagement. Covalent aptamers are new tools that enable specific protein modification and sensitive protein detection. Moreover, they provide prolonged, nuclease-resistant enzyme inhibition.

Automated summary

This new approach selectively modifies native proteins in their biological environment using electrophilic covalent aptamers, providing high target specificity and broad programmability. Covalent aptamers address issues such as instability and offer advantages in protein modification and detection, as well as nuclease-resistant enzyme inhibition.