Flavinyl peptides. I. Synthesis of flavinyl‐aromatic amino acids

Abstract

AbstractThe syntheses of flavinyl peptides, in which L‐tryptophan, L‐tyrosine, or L‐phenylalanine are attached via peptide linkage to the isoalloxazine system with ω‐carboxyalkyl groups in position 3 or 10, are described. Lumiflavin was carboxymethylated by known methods to yield N‐3‐carboxymethyllumiflavin. Oxidation of 10‐ω‐hydroxyhexyl‐, 10‐ω‐hydroxypentyl‐, 10‐ω‐hydroxybutyl‐, and 10‐formylmethylflavins gave the corresponding 10‐ω‐carboxyalkylflavins. The 10‐ω‐carboxyethylflavin was obtained by condensation of 2‐amino‐4,5‐dimethyl‐N‐ω‐carboxyethylaniline with alloxan. Activations of the carboxyl group of the flavins were achieved with N,N′‐carbonyldiimidazole and p‐nitrophenyltrifluoroacetate to form the corresponding acyl imidazoles and p‐nitrophenyl esters. 10‐Carboxymethylflavin was hydrogenated to form 10‐carboxymethyldihydroflavin and activated by carbodiimide. Reaction of the carboxy‐activated flavins with the appropriate amino acid methyl esters, followed by air oxidation in the case of dihydroflavin, gave the corresponding flavinyl peptides.Interaction of the flavin with aromatic amino acids results in a broadening of the visible flavin absorption towards the green, without the appearance of discrete new maxima, and in quenching of the flavin fluorescence. The fluorescence efficiency increases with increasing numbers of methylene groups in the flavin side chain. The nonlinear dependency of fluorescence quenching versus number of methylene groups indicates that different types of intramolecular interactions are involved.