Can the 1,5-disubstituted tetrazole ring modify the co-ordinating ability and biological activity of opiate-like peptides?

The copper(II) complexing ability and the biological activity of beta-casom orphin-7 tetrazole analogues have been investigated. Potentiometric and spe ctroscopic (UV-Vis, CD and EPR) studies have been used to establish the the rmodynamic 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-N H2 (3). Comparison of the binding ability of the tetrazole analogues reveal s that the most effective ligand for copper(II) is YPF-psi(CN4)-AGPI-NH2. T he effectiveness of this ligand comes from its particular conformation suit ed 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 h istamine release in vitro in the presence of copper(II) has been studied. ( C) 2000 Elsevier Science Inc. All rights reserved.