Cyclic peptides. 23. Conformations of an ion-binding cyclic peptide analog of valinomycin, cyclo(L-Val-Gly-Gly-L-Pro)3

Abstract

A 270-MHz 1H nuclear magnetic resonance investigation of an ion-binding cyclic peptide analogue of valinomycin, cyclo(L-Val-Gly-Gly-L-Pro)3, and its cation complexes is reported. In CD2Cl2 and CDCl3, the peptide is proposed to occur in a C3-symmetric conformer with the N--H's of all six glycine residues intramolecularly hydrogen bonded. This conformation is different from the familiar valinomycin bracelet structure and lacks any "cavity". Cations do not bind, or bind only weakly, to the peptide in these solvents. Uncomplexed cyclo(L-Val-Gly-Gly-L-Pro)3 in acetonitrile appears to be averaging among several conformations with no evidence found for any preferred intramolecular hydrogen bonds. The strong 1:1 complexes of cyclo(L-Val-Gly-Gly-L-Pro)3 with K+ ANd Ba2+ in acetonitrile are structurally analogous to the bracelet conformation of valinomycin and involve the N--H's of the Val residues and of the Gly's preceding Pro in intramolecular hydrogen bonding. Tl+ was also found to form strong 1:1 complexes with the dodecapeptide.

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.…”