Conformation of uncomplexed [Phe4, Val6] antamanide crystallized from nonpolar solvents.

Abstract

[Phe4,Val6]antamanide, a synthetic, biologically active analog of the cyclic decapeptide antitoxin isolated from Amanita phalloides, was crystallized from a mixture of n-hexane and methyl acetate, and its conformation was established by the direct method of x-ray diffraction analysis, i.e., without the benefit of any heavy atom. The uncomplexed molecule contains a 2-fold rotation axis and cis peptide linkages between Pro2-Pro3 and Pro7-Pro8. Otherwise, its conformation differs extensively from that of the Na+[Phe4,Val6]antamanide-.cntdot.C2H5OH complex. The 30-membered ring is elongated and relatively planar as compared to the folded ring in the Na+ complex. The 6 NH groups are directed toward the interior of the molecule. There is 1 pair of intra-molecular NH.cntdot..cntdot..cntdot.O.dbd.C bonds of the 5 .fwdarw. 1 type containing a cis peptide unit. The other 4 NH groups participate in H bonds to 3 H2O sites in the interior of the molecule. The 10 hydrophobic side groups cover the bottom and surround the perimeter of the molecule with the phenyl groups in the 4 Phe residues folded against the molecule. The conformation found for [Phe4,Val6]antamanide crystallized from nonpolar solvents is different from any conformations proposed for antamanide in solution based on NMR data.