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

Abstract

The 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.

Interactions of Flavins With Amino Acid Residues: Assessments From Spectral and Photochemical Studies

“…The efficiency decreases markedly in a nonlinear fashion with decreasing chain length between interacting moieties, as seen in Fig. 4, where only a fraction of the fluorescence, compared to free flavin in different solvents, remains (Fory et al, 1968;MacKenzie et al, 1969). The effect of increasing temperature, which leads to disruption of quenched complexes but increases collisional quenching, is seen in Fig.…”

“…Most often, such spectroscopic models, shown in Fig. 2, have been synthesized by amide-linking the amino acid or its ester to o-carboxyalkyl chains of 7,8-dimethylisoalloxazines substituted at positions N' O or N3 (Fory et al, 1968).…”

Volume changes in the formation of internal complexes of flavinyltryptophan peptides

“…The connecting chain in these peptides is much shorter than in FAD. Their synthesis and some spectral properties have already been reported (Fory et al, 1968;MacKenzie et al, 1969).…”

Repair of UV Light Induced DNA Lesions: A Comparative Study with Model Compounds

“…[80] Initial measurements of model compound 39 show tion < 0.1) are now in progress to evaluate its magnitude in that the flavin fluorescence is strongly quenched in the presorder to precisely determine to which extent the deazaflav-ence of the electron-rich tryptophane residue. [106] Reins influence the splitting efficiency in our model com-duction of the flavin unit with sodium dithionite could, pounds.…”