Genetically encoded unnatural amino acids (Uaas) provide new chemical tools that can be site selectively incorporated into proteins. This offers the potential for addressing biological questions at the molecular and cellular level. Uaas can be genetically incorporated into proteins using orthogonal tRNA-codon–synthetase sets. Our efforts have been focused on designing and synthesizing new fluorescent Uaa's and improving their incorporation efficiency. Here, we show the successful incorporation of the Uaa acridonylalanine (Acd) into E. coli cells with minimal perturbation to the protein of interest. A new Acd derivative of interest is 2-aminoacridonylalanine (Aad), which has a substantially red-shifted emission in comparison to Acd. While Aad is a possible candidate FRET acceptor for chromophores such as methoxycoumarin and Acd, it has a relatively low quantum yield. Therefore, we are synthesizing new derivatives that are 3-4 times brighter than Aad. We additionally are synthesizing and testing novel ester derivatives of the Uaas for improved uptake and incorporation in both mammalian cells and E. coli. Our long-term goal is the development of a palette of fluorescent Uaas across the spectrum that can be fully genetically encoded to facilitate the monitoring of protein processes.

Design, synthesis, and development of new fluorescent unnatural amino acids for genetic incorporation into proteins

Macromolecular Chemistry: The Second Century

[Author Benefits](https://scimeetings.acs.org/?utm_source=pubs_content_marketing&utm_medium=website&utm_campaign=0320_MCF_NPI_Launch_Spring_Homepage&ref=pubs_content_marketing)

[How to use SciMeetings](https://storage.googleapis.com/dl.morressier.com/acs/SciMeetings-ACSSpring2020-HowToGuide_M3020-Final.pdf)

[Frequently Asked Questions](https://storage.googleapis.com/dl.morressier.com/acs/SciMtng_ACSNMSp2020_FAQ_M3120_Final.pdf)

ACS Spring 2020 National Meeting & Expo

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