On the Interaction between Flavin and Indole Rings. Crystallographic, Spectroscopic, Polarographic and Energy Calculational Studies of a Flavinyltryptamine Peptide

As an intramolecular model for flavin-indole interaction, the crystal structure of N-2-(3-indolyl)ethyl-7, 8-dimethylisoalloxazine-10-propionamide, a flavinyltryptamine peptide, was determined by the X-ray diffraction method. Although the molecule took an open conformation without indole-flavin interaction, this could be a result of crystal packing effects, because ultraviolet and fluorescence data showed the existence of a prominent intramolecular stacking interaction of the rings in aqueous solution. Proton nuclear magnetic resonance analysis indicated a preferential stacking interaction between the indole ring and the pyrazinoid and pyrimidinoid portions of the flavin ring. These results were supported by the conformation analysis of this molecule based on energy calculations. Polarographic data showed that the indole ring affects the reduction state of the flavin semiquinone form to the hydroquinone form. The results suggest that a tryptophan residue of a flavin enzyme might act not only to fix the flavin coenzyme in place, but also to stimulate the reduction reaction.