Efficient Syntheses of a Flavin and an 8-Hydroxy-5-deazaflavin Amino Acid and Their Incorporation into Oligopeptides

Abstract

We report a convenient synthesis for the cofactor amino acids (S)-3 and (S)-4 in which the C5-ribose chain of the original riboflavin and ribo-5-deazaflavin cofactors is replaced by a C5-amino acid side chain. Both cofactor amino acids are available in enantiomerically pure form in gram quantities and can be incorporated into oligopeptides using a standard Fmoc-based solid-phase peptide synthesis protocol. The benzyl-protecting group of the 8-hydroxy-5-deazaflavin can be cleaved by hydrogenolysis directly on the peptide. This allows the investigation of the properties of the peptide bound redox active OH- and the deprotonated O--form of the deazaflavin. Due to the electron- and energy-transfer properties of both cofactors, applications of both amino acid in the preparation of peptide- and protein-based biosensors, of catalytically active peptides, or as chemical rulers for distance measurements in biopolymers based on the fluorescence resonance energy-transfer technology can be envisaged.