Unusual gain in the coordination ability of vasopressin-like peptides towards Cu2+ ions by insertion of the highly hydrophobic side chain

Abstract

Potentiometric and spectroscopic data show an unusual gain in the stability constants of Cu²⁺ complexes with vasopressin analogues having the highly hydrophobic naphthalene-alanine residue inserted in position three (Nal³). The naphthalene derivative is a much more powerful ligand for binding Cu²⁺ ions that the parent peptide. Theoretical calculations indicate the effective hydrophobic protection of the metal site by Tyr² and Nal³ aromatic side-chains. The interaction of the guanidine moiety of Arg⁴ with naphthalene can also increase distinctly the stability of the respective 4N complex.