Peptide ionophores: synthesis and cation-binding properties of a bicyclic peptide containing glycine and lysine residues.

Abstract

Peptide 1, cyclo(1,5-epsilon-succinoyl) (Lys-Gly-Gly-Gly)2, is a representative member of a family of polycyclic peptide ionophores characterized by C2 symmetry and a relatively flexible structure resulting from its high Gly content. Peptide 1 has been synthesized by two different solid-phase protocols from its linear precursors, H-Gly-Gly-Lys(Fmoc)-Gly-Gly-Gly-Lys(Fmoc)-Gly-OH and H-Gly-Gly-Lys(Z)-Gly-Gly-Gly-Lys(Z)-Gly-OH), and satisfactorily characterized by chemical means. The CD spectrum of 1 is compatible with a beta-folded structure, stabilized by two internal hydrogen bonds. The complexation behavior of 1 toward alkaline and alkaline-earth cations can be envisaged as an equilibrium between inclusion (1:1) and sandwich (2:1) complex models, with affinities in the 10(6) M-1 and 10(11) M-2 range, respectively. A slight preference of 1 for Sr2+ over other cations has been found.