Cation‐binding cyclic peptides with lipophilic tails

We have synthesized and characterized a series of cation‐binding cyclic octapeptides which may function as potential ionophoric substances. The materials contain varying degrees of hydrophobic character, which was controlled systematically through the incorporation of N‐alkylglycine residues where N‐alkyl = methyl, n‐hexyl, cyclohexyl, or n‐decyl. The peptides reported include cyclo(Phe‐Sar‐Gly‐Sar)2, cyclo(Glu(OBzl)‐Sar‐Gly‐Sar‐Glu(OBzl)‐Sar‐Gly‐(N‐decyl)Gly), cyclo(Glu(OBzl)‐Sar‐Gly‐(N‐decyl)Gly)2, cyclo(Glu(OBzl)‐Sar‐Gly‐(N‐hexyl)Gly)2, cyclo(Glu(OBzl)‐Sar‐Gly‐(N‐cyclohexyl)Gly)2, and the corresponding free diacid forms of the Glu‐containing compounds. Using 13C‐ and 1H‐nmr spectra, we demonstrated that the mixture of cis/trans peptide bond‐isomer conformers, characteristic of the free‐peptide benzyl esters in solution, was converted to unique C2‐symmetric, presumably all‐trans conformers on complexation with calcium ions. Cation‐transport experiments, using the thick‐liquid model of transport in a Pressman cell, established that these compounds transport a variety of cations and that one peptide examined in detail, cyclo(Glu(OBzl)‐Sar‐Gly‐(N‐decyl)Gly)2 (selectivity Ca2+ > Na+ > K+ > Mn2+ > Cu2+ > Mg2+ > Co2+ > Zn2+), transports calcium about an order of magnitude more efficiently than magnesium.