Premium
Protein Labeling and Crosslinking by Covalent Aptamers
Author(s) -
Tivon Yaniv,
Falcone Gianna,
Deiters Alexander
Publication year - 2021
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.202101174
Subject(s) - aptamer , covalent bond , nuclease , chemistry , combinatorial chemistry , electrophile , target protein , biochemistry , nanotechnology , enzyme , biology , microbiology and biotechnology , gene , materials science , organic chemistry , catalysis
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.