Decapeptide, cyclic, antamanide

In a shortened synthesis program one can combine the wash-out of the urea derivative with the subsequent deprotection reaction [61]. The acidic reagents used on that step, such as trifluoroacetic acid/dichloromethane or hydrogen-chloride/acetic acid, are excellent solvents for the urea by-product. Under these circumstances, however, the repetition of the actual peptide synthesis step, which eventually enhances its completion, is no longer possible, since the next cycle of operations is already initiated with the N-terminal deprotection of the just elongated sequence. We utilized this time-saving, shortened program successfully in the synthesis of several uncomplicated decapeptide precursors of the cyclic antamanide from Boc-amino acids. 

The amatoxins are cyclic octapeptides composed only of L-amino acids and containing a sulfoxide group instead of the thioether bridge in phallotoxin. Over 90% of the fatal cases of mushroom poisoning can be traced back to the amatoxins. Wieland et al. 234) have shown that, in addition to the toxins, the death cup contains a low concentration of an antitoxic cyclic decapeptide antamanide 108. 

Antamanide is a cyclic decapeptide antibiotic represented as Cyclo Val -Pro -Pro .Ala -Phe -Phe T>ro -Pro -Phe -Phe ). Antamanide also forms very stable complexes with Li and K in nonpolar solvents such as acetonitrile. Hie 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 Pig. 32, where the fifth ligand for Li is solvent acetonitrile. This... 

Another compound studied was antamanide. It is a cyclic decapeptide isolated from amanita phalloides. Its structure was determined by Th. Wisland and his coworkers 34). This compormd was also found to have carrier properties, however with a pronounced Na+ specificity. The relaxation time of the complex formation process between antamanide and Na+ is in the millisecond range 35). It could therefore be investigated by means of the T-jump technique. 

N-Methylmorpholine [1, 690]. In the mixed anhydride synthesis of peptides, N-methylmorpholine was found to give little or no racemization in cases where triethylamine, the commonly used base, caused extensive racemization.1 Trimethyl-amine, a potent racemizer, can be used successfully if an excess is avoided. N-Methylmorpholine was used by Wieland2 in the synthesis of antamanide, a cyclic decapeptide of Amanita phalloides, which counteracts the lethal action of Amanita toxins. 

The extremely poisonous green mushroom Amanita phalloides contains a number of cyclic peptides classified as phallotoxins (heptapeptides), ama-toxins (octapeptides), and a decapeptide antagonist called antamanide (Wieland and Wieland, 1972). Crystal structure analyses have been completed on jS-amanitin, on antamanide, and on a biologically active analog, both com-plexed and uncomplexed. 

L-Phe and in the cyclic decapeptide antamanide have been demonstrated. 

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. 

Syntheses on polymer support are of invaluable merit in the preparation of linear structures of about decapeptide size — e.g., the bradykinins — and of precursors for cyclic structures as in the case of gramicidin S, oxytocin, vasopressin, and the antamanides. 

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... 

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