Ca2+ binding cyclic octapeptides having an alternating sar and a hydrophobic amino acid in the sequence

Abstract

Cyclic octapeptides having alternating Sar and hydrophobic amino acid sequences, such as cyclo[Lys(Z)-Sar-Leu-Sar-Leu-Sar-Leu-Sar] (C8KL), cyclo[Glu(OMe)-Sar-Lys(Z)-Sar-Leu-Sar-Leu-Sar] (C8KE, and cyclo[Lys(Suc)-Sar-Leu-Sar-Leu-Sar-Leu-Sar] [C8K(Suc)L, Suc represents succinic acid], were synthesized. These cyclic octapeptides formed a complex selectively with Ca2+. Upon complexation, trans peptide bonds of Sar residues were isomerized to cis peptide bonds. C8KL and C8KE showed very similar characteristics of Ca2+ binding, extraction of Ca2+ from an aqueous solution to a chloroform solution, and Ca2+ transport through a liquid chloroform membrane. C8KL transported Ca2+ across the lipid bilayer membrane above the phase-transition temperature, while C8KE and C8K(Suc)L did not. Therefore, the transport of Ca2+ through the lipid bilayer membrane is very sensitive to the hydrophobicity of the carrier molecule.