Selective ion transport and ion extraction by synthetic cyclic octapeptide

Cyclic octapeptide, cycloGly-L-Lys(Z)-Sar-L-Pro]₂ (CGLSP2) was synthesized as an ionophore model. Its ion-transport ability through a liquid membrane was investigated in connection with ion extractability and conformational properties. CGLSP2 transported the picrate salts of Ba²⁺ and Ca²⁺ efficiently through chloroform membrane in a U-tube (Ba²⁺> Ca²⁺ > K⁺ > Rb⁺ > Mg²⁺> Na⁺). CycloGly-L-Lys(Z)-Sar-L-Pro] or Boc-Gly-L-Lys(Z)-Sar-L-Pro]_n-OR (n = 1 or 2; R = H or CH₃) showed a significant decrease in ion-transport ability. Extraction equilibrium constants (K_ex) of CGLSP2 with metal picrates were determined in chloroform-water system. In this case, CGLSP2/cation complexes were found to have a stoichiometry of 1:1. The K_ex sequences were Ba²+ > Ca²⁺ > Mg²⁺ and K⁺ > Rb⁺ > Na⁺, showing good agreement with the selectivity in ion transport. Conformation of CGLSP2 in chloroform (CDC1₃) was investigated by ¹H and ¹³C-n.m.r. spectroscopy. Predominant conformation takes a C₂ -symmetric structure containing two cis Lys-Sar peptide bonds. Upon complexation with Ca²⁺ in CDC1₃/CD₃CN mixture (5/3, v/v), the conformation of CGLSP2 converged into a single C₂ -symmetric one that was predominant in a free state in CDC1₃.