Synthetic flavinyl peptides related to the active site of mitochondrial monoamine oxidase. I. Chemical and spectral properties

Abstract

Various 8 alpha-sulfur-linked peptides related to the flavinyl peptides isolated from mitochondrial monoamine oxidase were synthesized in high yield and purity. The peptides, protected by an acetyl-blocking group on the amino terminus, were synthesized by conventional liquid-phase techniques and coupled to a tetraacetylriboflavin derivative activated in the 8alpha position. In some cases, the ribityl side chains of the flavinyl peptides were selectively deacetylated. In other cases, the thioether functions were oxidized to form sulfones. These flavinyl peptides were studied by uv-visible absorption and circular dichroic spectroscopies. A close correspondence in spectroscopic and other chemical properties indicated the identity of the synthetic and naturally obtained flavinyl peptides. Differences between the tetraacetylriboflavinyl and riboflavinyl peptides indicate an interaction between the ribityl side chain and thioether function in aqueous media. Evidence was obtained for an intramolecular complex between the tyrosyl and isoalloxazine moieties in aqueous media. Substitution in the 8alpha position was accompanied by an impairment of the protonation of the N1 position of the isoalloxazine ring and a lowering of the redox potential relative to the parent 8-methyflavins.