Cyclic Peptides with Metal Cations

Interactions of Cyclic Peptides with Metal Cations 

For examfde, cyclic dodecadepsipeptide antibiotic valinomycin (18) is represented as Cyclo D-Val-Lac-Val-D-ifyv)3 where Lac and Hyv re esent lactic acid and a-oxyisobutyric add, re ctively. ValinoiiQrcin selectively binds K, when it acts as an antibiotic. As shown in Fig. 31, valinomycin takes a bracelet structure and has a cavity in the middle with a diameter of 6—7A. Sizes of hydrated cations are 4.5—5.0 A for K, Rb, and Cs and 5.5—7.4 A for Na and Li . It is understandable that the cavity fits in with K. Carbonyl groups are distributed along the inside wall of the cavity which is necessarily polar. Alifdiatic side chains form the outside wall of the bracelet whidi is necessarily nonpolar. Valinomycin binds in the hydro-0ulic interior of the cavity and transports the ion across the lipid bilayer of the cell 

Antamanide is a cyclic decapeptide antibiotic represented as Cyclo-(Val -Pro -Pro -Ala -Hie -Phe -Pro -Pro -Phe -Phe °). Antamanide also forms very stable complexes with Li and K in nonpolar solvents such as acetonitrile. The crystalline structure of Li -antamanide complex has been investigated 137). It has been made clear that two peptide bonds Pro -Pro and Pro -Pro are cis, there are two intramolecular hydrogen bonds, and four carbonyl groups coordinate to Li. This structure is depicted in Fig. 32, where the fifth ligand for Li is solvent acetonitrile. This 

Pheib have been ommitted for clarity. iTaken from Fig. 2 of Ref. (257)1 

Emphasis has so far been placed on items (i) and (ii). The investigations, which will be described subsequently, were aimed at the following three points (i) the 

As schematically own in Fig. 30, the cell membranes of living organism (/ S6) are composed of a lipid bilayer and form the interface between the intracellular and the extracellular aqueous parts. Concentrations of metal ions and amino adds in the cell are thus kept constant and the biological functions in the cell are executed. Specifically, the concentration of metal ions is in a dynamic equilibrium between the inside and the outside of the cell membrane, and it has been suggested that the mass tran rt through the membrane is mediated by lipoproteins. For the metal-km tran rt through the membrane, the participation of a group of cyclic conqxrunds called lonophores is important, which is dosely related to the antibiotic actions of cyclic peptides and cyclic depsipeptides (iJ6). These cyclic compounds are compatibile 

For examfde, cydic dodecadepsipeptide antibiotic valinomycin (18) is refure-sented as Cydo-(D-Val-Lac-Val-D-Ifyv)3 where Lac and Hyv re esent lactic add and cr-oxyisobutyric add, re ctively. ValinonQrcin selectively binds K, when it acts as an antibiotic. As shown in Fig. 31, valinomycin takes a bracelet structure and has a cavity in the middle with a diameter of 6—7A. Sizes of hydrated cations are 

---

JL Interactions of Cyclic Peptides with Metal Cations... 

The interaction between cyclic peptides and metal cations is closely related to their activities as antibiotics and to ion transport processes. An example of such interaction by a cyclic dipeptide is the complex formed by Li and cyc/o(Sar)2. The Li forms four Li" —O ligands (the length of which is near 1.92 A) with the C=0 groups of four independent cyc/o(Sar)2 molecules that surround the Li" in a tetrahedral array. The other C=0 of each dipeptide coordinates to another Li" to make an infinite two-dimensional network in the crystal (Takahashi et a/., 1977). 

---