Poster Presentation International Peptide Symposium 2023

Genetic Encoding of 7-Aza-L-Tryptophan: Isoelectronic Substitution of a Single CH-Group in a Protein for a Nitrogen Atom (#203)

Elwy H. Abdelkader 1 , Haocheng Qianzhu 2 , Thomas Huber 2 , Gottfried Otting 1
  1. ARC Centre of Excellence for Innovations in Peptide & Protein Science, Research School of Chemistry, Australian National University, Canberra, ACT 2601, Australia
  2. The Research School of Chemistry, The Australian National University, Canberra, ACT 2601, Australia

Genetic code expansion (GCE) via stop codon suppression is a powerful technique for studying biological macromolecules. This technique enables the precise installation of different functionalities into peptides and proteins through the site-specific incorporation of non-canonical amino acids (ncAA). We succeeded in genetically encoding the isoelectronic tryptophan analogue 7-azatryptophan (7AW), leading to proteins with a single CH-group substituted for a nitrogen atom. 7AW is readily synthesized enzymatically from serine and 7-azaindole using tryptophan synthetase β-subunit (TrpB). Using 15N/13C-labeled 7AW, the NMR resonance peak assignments of the tryptophan residues in Zika virus NS2B-NS3 protease was achieved.

  1. E. H. Abdelkader, H. Qianzhu, J. George, R. L. Frkic, C. J. Jackson, C. Nitsche, G. Otting, T. Huber, Angew Chem Int Ed Engl 2022, 61, e202114154
  2. H. Qianzhu, E. H. Abdelkader, I. D. Herath, G. Otting, T. Huber, ACS Sens 2022, 7, 44-49