Antamanide conformation

A precise calculation of AGd as a function of the cationic radius would be very difficult because it would involve a complete conformational analysis of a large and complicated ligand system (82). Nevertheless, the dependency of the cation selectivity on steric interactions is capable of illustration. The term AGd can be estimated very crudely by using Hooke s law. As is shown in Fig. 16, ligands that are differentiated only by the radius of their equilibrium cavities can easily discriminate between cations of different size. This may explain why valinomycin and antamanide, two antibiotics with similar coordination spheres (54, 66), do not prefer the same cation (82). As it is no easy task to predict the exact dimensions of the cavity for a proposed ligand, the tailored synthesis of such ligands is conceivable yet problematic. 

Molecular Dynamics Simulation of the Proline Conformational Equilibrium and Dynamics in Antamanide Using the GROMOS Force Field. 

Fig. 39. Conformation of [Phe4, Val6] antamanide, crystallized from non-polar solvents. The water molecules associated with the peptide are labeled Wj, and hydrogen bonds are indicated by light lines [Reproduced from Karle, I. L., et al Proc. Nat. Acad. Sci. USA 73, 1782 (1976).]...

Preliminary X-ray analytical data of [Phe4, Val6] antamanide, crystallized from organic solvent-water mixtures, indicate that in polar solvents the peptide assumes a conformation different from either the one in non-polar solvents or in the com-... 

Elucidation of the complex conformation of antamanide has also been a gradual process. From the first analysis on the basis of IR, ORD, and NMR spectra, a bracelet conformation similar to the valinomycin-K+ complex was proposed, possessing all-... 

Fi. 40. Conformation of the antamanide-Li complex, crystallized from acetonitrile. The phenyl groups of Phe5 and Phe10 have been omitted for clarity. 

Fig. 32. Conformation of Li -antamanide complex. ( ), K (crrd), backbone of antamanide ...

The conformation of uncomplexed antamanide is entirely different from that of the alkali metal ion complexes. Not only is the cyclic backbone elongated and flattened, but sequences 4,5,6 and 9,10,1 turn inside-out so that the... 

Valinomycin, a cyclic 12-depsipeptide with the sequence cyc/o(LVal-DHyv-DVal-LLac)3, selectively transports K ions across natural and synthetic membranes. The conformations of the K complex and the uncomplexed form of valinomycin are different, but not as markedly different as the com-plexed and uncomplexed forms of antamanide. The molecular formula of valinomycin exhibits a threefold symmetry, which is maintained in the crystalline state for the K complex. If the differences in the side chains are overlooked, the approximate symmetry is raised to An early crystal structure determination of the KAUCI4 complex (Pinkerton et al, 1969) established that the ion is octahedrally coordinated to the carbonyl oxygen atoms of the six ester groups and that the carbonyl oxygen atoms from the six amide groups form hydrogen bonds with the six NH moieties (4 1 type... 

As mentioned in Chap. 9 (p. 215) the cyclic decapeptide antamanide exists in several conformations depending on the presence or absence of alkali metal ions and on the polarity of the solvents. The transition of the free form to a complexed one can be easily followed by CD spectra (Fig. 7). On the addition of Na ions or water the large negative ellipticity (Cotton effect) observed in apolar solvents, such as dioxane, disappears and changes into a positive Cotton effect in the same wave length region. 

One or more stable conformations can also be assumed for cyclic peptides which can adopt more or less rigid structures stabilized by hydrogen or other bridges or, strongly, by complexing various metal ions. As an example of many published structures [41], there is the Li-complex of the antitoxic mushroom peptide antamanide (see p. 215), a structure which was determined in 1973 by Isabella L. Karle [42] using the direct method of Jerome Karle (Nobel Prize 1987, shared with J.A. Hauptmann). 

I. Karle, K. Karle, Th. Wieland, W. Burgermeister, H. Faulstich, B. Witkop, Conformation of the Li-antamanide complex and Na- (Phe, Val )-antamanide complex in the crystalline state, Proc. Natl. Acad. Sci. USA 70 1836-1840 (1973)... 

W. Burgermeister, Th. Wieland, R. Winkler-Oswatitsch. Antamanide. Relaxation study of conformational equilibria, Eur. J. Biochem. 44 311-316 (1974)... 

H. Kessler, J.W. Bats, J. Lautz, A. Muller, Conformation of antamanide, Liebigs Ann. Chem. 1989 913-928... 

J.M. Schmidt, Conformational equflibria in polypeptides. II. Dihedral-angle distribution in antamanide based on three-bond coupling information, J. Magn. Reson. 124 (1997) 310-322. 

Antamanide. Antamanide is a cyclic decapeptide which occurs in the Amanita mushroom. Karle has determined and refined the structures of crystals of a complex of antamanide with lithium and of a complex of an analog of antamanide with sodium [37, 38]. Antamanide has a cyclic backbone it contains four proline residues, and four of its oxygens are ligands of the ion. Consequently, the conformation of antamanide is compact and shows a number of nonbonded contacts. The molecule is quite hydrophobic, and the crystal structure forms a hydrophobic matrix of antamanide... 

Fig. 4. Conformation of lithium antamanide after Karle [37]. Different portions of the molecule are shown in different shadings.

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