ABSTRACT
The copper(II) complexing ability and the biological activity of beta-casomorphin-7 tetrazole analogues have been investigated. Potentiometric and spectroscopic (UV-Vis, CD and EPR) studies have been used to establish the thermodynamic stability, speciation and structure of Cu(II) complexes with YP-psi(CN4)-FPGPI-NH2 (1), YPF-psi(CN4)-AGPI-NH2 (2) and YPFP-psi(CN4)-GPI-NH2 (3). Comparison of the binding ability of the tetrazole analogues reveals that the most effective ligand for copper(II) is YPF-psi(CN4)-AGPI-NH2. The effectiveness of this ligand comes from its particular conformation suited for the Cu(II) 2N co-ordination mode in the physiological pH region. The ability of casomorphin tetrazole analogues to activate rat mast cells to histamine release in vitro in the presence of copper(II) has been studied.
Subject(s)
Endorphins/pharmacology , Narcotics/chemistry , Oligopeptides/chemical synthesis , Oligopeptides/pharmacology , Peptides/metabolism , Tetrazoles/chemistry , Tetrazoles/chemical synthesis , Tetrazoles/pharmacology , Animals , Circular Dichroism , Copper/metabolism , Electron Spin Resonance Spectroscopy , Endorphins/chemistry , Histamine/biosynthesis , Hydrogen-Ion Concentration , Ligands , Mast Cells/drug effects , Mast Cells/metabolism , Models, Chemical , Peptides/chemistry , Protein Binding , Protein Conformation , Protein Structure, Secondary , Rats , Spectrophotometry , Thermodynamics , Ultraviolet RaysABSTRACT
A study of the effect of the tetrazole moiety, a cis-amide bond surrogate, on the Cu(II) coordinating properties of oligopeptides is reported. The insertion of the tetrazole moiety psi (CN4) into the peptide sequence of [Leu5]enkephalin considerably changes the coordination ability of the ligand. Potentiometric and spectroscopic results indicate that if the tetrazole moiety is in a suitable position in the peptide chain, i.e. if it follows the third residue, an unusual stable CuH-1L species involving 4N coordination is formed in the physiological pH region. The tetrazole psi (CN4) ring provides one of these nitrogens. The data indicate that Cu(II) ions are strongly trapped inside a bent peptide backbone. However, the coordination mode involving the tetrazole ring nitrogen does not prevent the hydrolysis process under strongly basic conditions.
Subject(s)
Copper/chemistry , Enkephalin, Leucine/analogs & derivatives , Enkephalin, Leucine/chemistry , Amino Acid Sequence , Circular Dichroism , Electron Spin Resonance Spectroscopy , Hydrolysis , In Vitro Techniques , Ligands , Protein Conformation , Protons , Spectrophotometry , Spectrophotometry, Ultraviolet , Tetrazoles/chemistryABSTRACT
The alpha-casein peptide fragment (90-96) Arg-Tyr-Leu-Gly-Tyr-Leu-Glu, one of the exorphins called "food hormones", is an efficient ligand for Cu(II) ions. Potentiometric and spectroscopic studies on aqueous solutions indicate that, depending on the pH range, complex species with different coordination modes (involving the amino and the deprotonated amide groups) are formed. The phenolate side chain of the Tyr residue is not involved in the metal coordination.
