The amino acid acridonylalanine (Acd) can be a valuable tool for studying protein dynamics. On its own, Acd’s long fluorescence lifetime of 15 ns has been beneficial for polarization experiments to reveal protein binding dynamics in biological pathways. Acd can also reveal structural dynamics as part of a Förster resonance energy transfer (FRET) or photoinduced electron transfer (PET) probe pair.  We have reported successful, selective genetic incorporation of Acd by an aminoacyl tRNA synthetase. This allows us to site-specifically label a protein of interest expressed in <i>E. coli</i> with minimal perturbation. We have developed new Acd derivatives that can shift Acd’s fluorogenic properties while still being ribosomally permitted for genetic incorporation. One derivative has been shown to be an enhanced FRET acceptor in a peptide cleavage assay and can be activated by the existing Acd tRNA synthetase for genetic incorporation. We are working to evolve aminoacyl tRNA synthetases to improve the incorporation of new Acd derivatives. We additionally are testing a new series of tRNA synthetases suitable for Acd incorporation in mammalian cells. Our long-term goal is to develop FRET pairs that can be completely genetically encoded to enable monitoring of protein processes that cannot be accessed with other labeling methods, such as real-time monitoring of co-translational protein folding.

Development of intrinsically fluorescent unnatural amino acids for <i>in vivo</i> incorporation into proteins

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.

Development of intrinsically fluorescent unnatural amino acids for in vivo incorporation into proteins