The structural effects of the Cys-S-S-Cys bridge exchange by the His-Cu(II)-His motif studied on natural peptides - A promising tool for natural compounds-based design

A replacement of both Cys residues by His in oxytocin (OXT) sequence allows for the formation of the stable complex with the {NH₂, 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.