Selective ruthenium labeling of the tryptophan residue in the bee venom Peptide melittin.

Melittin is a membrane-active peptide from bee venom with promising antimicrobial and anticancer activity. Herein we report on a simple and selective method for labeling of the tryptophan residue in melittin by the organometallic fragment [(C5 H5 )Ru](+) in aqueous solution and in air. Ruthenium coordination does not disturb the secondary structure of the peptide (as verified by 2D NMR spectroscopy), but changes the pattern of its intermolecular interactions resulting in an 11-fold decrease of hemolytic activity. The high stability of the organometallic conjugate allowed the establishment of the biodistribution of the labeled melittin in mice by inductively coupled plasma MS analysis of ruthenium.

Simple synthesis of ruthenium pi complexes of aromatic amino acids and small peptides.

The interaction of [Ru(eta(6)-C(10)H(8))(Cp)](+) (Cp=C(5)H(5)) with aromatic amino acids (L-phenylalanine, L-tyrosine, L-tryptophane, D-phenylglycine, and L-threo-3-phenylserine) under visible-light irradiation gives the corresponding [Ru(eta(6)-amino acid)(Cp)](+) complexes in near-quantitative yield. The reaction proceeds in air at room temperature in water and tolerates the presence of non-aromatic amino acids (except those which are sulfur containing), monosaccharides, and nucleotides. The complex [Ru(eta(6)-C(10)H(8))(Cp)](+) was also used for selective labeling of Tyr and Phe residues of small peptides, namely, angiotensin I and II derivatives.