Impact of 1,5-disubstituted tetrazole ring on chelating ability of d-selective opioid peptide.

Complex formation between Cu(II) and three tetrazole analogues of opioid peptide - deltorphin I has been investigated. In potentiometric and spectroscopic (UV-Vis, CD and EPR) studies have been established the thermodynamic stability, speciation and structure of Cu(II) complexes with Tyr-d-Ala-Phe-Asp-Val-Val-Gly-NH2 (L1), Tyr-?(CN4)-Gly-Phe-Asp-Val-Val-Gly-NH2 (L2), Tyr-Gly-?(CN4)-Phe-Asp-Val-Val-Gly-NH2 (L3) and Tyr-d-Ala-?(CN4)-Phe-Asp-Val-Val-Gly-NH2 (L4). The site of the insertion of tetrazole moiety ?(CN4) into the peptide sequences has critical impact on their co-ordination ability. Comparison of the binding ability of the tetrazole analogues reveals that around physiological pH region the L3 and L4 are more effective ligands for copper(II) than L1 and L2. The peptide conformation changes achieved by Cu(II) co-ordination may be essential for binding of the tetrazole deltorphins at the opiate receptors.