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The coordination abilities of tetrapeptides containing beta-amino acids towards Cu(II) ions are presented. The studied tetrapeptides were: Ac-betaAlaHisGlyHis, betaAlaHisGlyHis, Ac-betaAspHisGlyHis, betaAspHisGlyHis, Ac-betaAspHisGly-dHis and betaAspHisGly-dHis. Thorough potentiometric titrations were carried out to establish the stoichiometry of the resulting metal-ligand complexes and the role of free -alphaCOO(-) side chain group in metal binding. The copper(II) coordination mode of the complexes was investigated by performing detailed spectroscopic analyses (UV-Vis, EPR, CD) in strict correlation with potentiometric measurements.

A replacement of both Cys residues by His in oxytocin (OXT) sequence allows for the formation of the stable complex with the {NH(2), N(Im), N(Im(macrochelate))} binding mode at the physiological pH. The detailed potentiometric and spectroscopic studies on the Cu(II) complexes of [His(1,6)]OXT, together with high resolution NMR investigations on 3D structures of Cu(II) complexes with [His(1,6)]OXT and [His(1,6)]AVP analogues are presented and discussed. Exchange of the Cys-S-S-Cys bridge by the His-Cu(II)-His motif is very promising, because the resulting complexes retain topological similarity to the native S-S bridged AVP and OXT at pH values corresponding to the physiological pH.

A new vasopressin analogue, [His1,6]AVP, was synthesized and characterized by potentiometric measurements as well as by UV-Vis, CD and EPR spectroscopy. At the physiological pH the peptide forms a stable complex with Cu2+ ions which is characterized by the {NH2, NIm, NIm(macrochelate)} binding mode. The replacement of both Cys by His residues in the vasopressin sequence results in a very significant increase in the efficiency of Cu2+ binding.