Efficient syntheses of a flavin and an 8-hydroxy-5-deazaflavin amino acid and their incorporation into oligopeptides

We report a convenient synthesis for the cofactor amino acids (S)-3 and (S) -4 in which the C-5-ribose chain of the original riboflavin and ribo-5-deaz aflavin cofactors is replaced by a C-5-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 sol id-phase peptide synthesis protocol. The benzyl-protecting group of the 8-h ydroxy-5-deazaflavin can be cleaved by hydrogenolysis directly on the pepti de. This allows the investigation of the properties of the peptide bound re dox 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 biosensor s, of catalytically active peptides, or as chemical rulers for distance mea surements in biopolymers based on the fluorescence resonance energy-transfe r technology can be envisaged.