A Scalable Synthesis of the Blue Fluorescent Amino Acid 4-Cyanotryptophan and the Fmoc Derivative: Utility Demonstrated with the Influenza M2 Peptide Tetramer

A scalable synthesis of the Fmoc-protected blue fluorescent amino acid, L-4-cyanotryptophan (W-4CN), that exploits an enantioselective phase transfer-catalyzed alkylation is reported. The red-shifted emission of water-exposed W-4CN residues was leveraged to investigate the solvation state of tryptophan (Trp) residues within the influenza M2 proton channel. The correlation of the channel's conformation (i.e., open or closed) with the fluorescence spectrum of a mutated W-4CN residue suggests that the channel's conformational state does not impact the hydration status of the Trp residues.

Automated summary

A scalable synthesis of a Fmoc-protected blue fluorescent amino acid, L-4-cyanotryptophan (W-4CN), was reported in this study. The study leveraged the red-shifted emission of water-exposed W-4CN residues to investigate the solvation state of tryptophan residues within the influenza M2 proton channel. The correlation between the conformation of the channel and the fluorescence spectrum of a mutated W-4CN residue suggested that the channel's conformational state does not affect the hydration status of the Trp residues.