Improving the fluorescent probe acridonylalanine through a combination of theory and experiment

Itthipol Sungwienwong, John J. Ferrie, Joomyung V. Jun, Chunxiao Liu, Taylor M. Barrett, Zachary M. Hostetler, Naoya Ieda, Amara Hendricks, Anand K. Muthusamy, Rahul M. Kohli, David M. Chenoweth, George A. Petersson, E. James Petersson

Research output: Contribution to journalArticlepeer-review

Abstract

Acridonylalanine (Acd) is a useful fluorophore for studying proteins by fluorescence spectroscopy, but it can potentially be improved by being made longer wavelength or brighter. Here, we report the synthesis of Acd core derivatives and their photophysical characterization. We also performed ab initio calculations of the absorption and emission spectra of Acd derivatives, which agree well with experimental measurements. The amino acid aminoacridonylalanine (Aad) was synthesized in forms appropriate for genetic incorporation and peptide synthesis. We show that Aad is a superior Förster resonance energy transfer acceptor to Acd in a peptide cleavage assay and that Aad can be activated by an aminoacyl tRNA synthetase for genetic incorporation. Together, these results show that we can use computation to design enhanced Acd derivatives, which can be used in peptides and proteins.

Original languageEnglish (US)
Article numbere3813
JournalJournal of Physical Organic Chemistry
Volume31
Issue number8
DOIs
StatePublished - Aug 2018
Externally publishedYes

Keywords

  • Acridone
  • amino acid
  • electronic structure calculation
  • fluorescence spectroscopy

ASJC Scopus subject areas

  • Physical and Theoretical Chemistry
  • Organic Chemistry

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