Conformation and complexation of a cyclic dodecapeptide [cyclo(L-Leu-L-Phe-L-Pro)4] with alkaline earth metal ions in acetonitrile

Abstract

The cyclic dodecapeptide, cyclo(L-Leu-L-Phe-L-Pro)₄, was synthesized, and its conformation and complexation with metal ions in acetonitrile were investigated by c.d. and n.m.r. spectroscopy. Cyclo(L-Leu-L-Phe-L-Pro)₄ was found to complex selectively with alkaline earth metal ions. The binding constant of the dodecapeptide with Ba²⁺ was larger than that of the cyclic hexapeptide, cyclo(L-Leu-L-Phe-L-Pro)₂. In a free state, the skeletal conformation of the cyclic dodecapeptide is non-symmetrical. When complexed with Ba²⁺, the conformation changes to a C₄-symmetrical one having all peptide bonds in a trans configuration and four β-turn structures containing transannular hydrogen bonds. Formation of hydrogen bonds on complexation with the cation accounts for the large binding constant of the cyclic dodecapeptide.