Cation binding cyclic peptides composed of imino acid residues

Abstract

SynopsisCyclo(L-Pro-Sar), (n = 2-4) with moderate flexibility and hydrophobicity of molecular structure was synthesized, and the characteristics of these cyclic peptides and their metal complexes in acetonitrile were investigated in connection with the residual properties using 13C-nmr measurements. The cyclic tetrapeptide cyclo(~-Pro-Sar)z showed a sterically hindered phenomenon in acetonitrile in which the amide backbone adopted a cis-trans-cis-trans sequence. The cyclic hexapeptide cyclo(~-Pro-Sar)~ existed as a mixture of several conformers whose interconversion is slow on the nmr time scale, including cis-cis-trans and/or cistrans-trans arrangement of the Sar-Pro bond. Finally, it was demonstrated that the cyclic octapeptide cyclo(L-Pro-Sar)4 behaved as a mixture of multiple conformers which allowed for cis-trans isomerism about the Pro-Sar peptide bond, of which 20-30% had the all-cis Sar-Pro bond isomer and the remaining 7040% had one (or more) cis Sar-Pro bond isomer. 13C-nmr spectra also demonstrated that cyclo(L-Pro-Sar), (n = 3,4) formed a 1:l ion complex whose conformation was characterized by an all-trans peptide bond in the presence of excess metal salt. Cation binding studies, using CD measurements, established that the ion selectivity of cyclo(L-Pro-Sar)4 in acetonitrile decreased in the order, Ba2+ > Ca2+ > Na+ > Mg2+ > Li+.

Solvation properties of natural and synthetic ionophores. I. Stoichiometry of complexes with alkali and alkaline earth cations in aprotic organic solvents

“…Cyclic-peptides in acetonitrile meet the criterion that DNaverage > DNsolvent. This is consistent with the formation of cation-sandwich and ligand-sandwich complexes of cyclic peptides with alkali and alkaline earth cations and ammonium salts in this particular solvent (23)(24)(25)(26)(27)(28)(29)(30).…”

“…connecting nonpolar, buried protein side chains), and so interactions of such groups (binding sites) with alkali and alkaline earth cations that tend to alter the free-energy difference between folded and unfolded forms of the macromolecule can certainly alter the stability of macromolecular conformations. The complexation studies of benzo-1 5-crown-5 with NaClO4 in nitro-methane (DNaverage > DNsolvent) and in diethyl ether, (DNaVeage = DNsolvent) together with experimental data of other studies of ionophores complexed with alkali and alkaline earth cations analyzed according to Table VI, support the above model (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33). Cyclic-peptides in acetonitrile meet the criterion that DNaverage > DNsolvent.…”

Multiple conformational equilibria of cyclic octapeptide, cyclo (L‐Pro‐Sar)4 in solution

“…Because 13C-n.m.r. measurement of this peptide indicated the coexistence of multiple conformers in acetonitrile as was expected 194 (10). The equilibria between a number of indicators to delineate the cis-trans isomerism conformers were ascribed to a cis-trans iso-around Sar-Pro peptide bonds.…”

“…EXPERIMENTAL PROCEDURES Alternatively, the N-methyl proton resonances of sarcosine became an important probe to clarify the symmetry of 24membered ring Cyclic octapeptide, cyclo (L-Pro-Sar),, was as well as the geometry around Pro-Sar pep-synthesized according to the method destide bonds. At the same time, the chemical cribed in a previous paper (10). The physical shifts of prolyl Cg and C, carbons were useful characteristics were given in that paper.…”

Crystal structure and conformation of a cyclic tetrapeptide cyclo(L‐Pro‐Sar)2 containing all‐cis peptide units

“…These are therefore potential candidates for "cis-allowed" Pro-Sar and Sar-Pro type peptide bonds. 15,16 For these reasons, it would be of great value to elucidate the crystal structure of conformationally interesting cyclic peptides.…”