Conformational stability of antamanide and analogs Crystal structure of perhydrosymmetric antamanide,cyclic (-Val-Pro-Pro-Cha-Cha-Val-Pro-Pro-Cha-cha-)

The synthetic perhydrogenated symmetric analog of the cyclic decapeptide antamanide is biologically inactive, although the conformation of the molecule and the crystal packing are very similar to that of the active symmetric analog of antamanide. In fact, the same conformation for the molecule has now been found in six polymorphs of uncomplexed antamanide and its analogs. The differences between the active and inactive antamanide analogs are displayed dramatically in the conformations of their metal ion (Na⁺ or Li⁺) complexes, thus suggesting strongly that for physiological activity antamanide is not in the conformation assumed by the uncomplexed molecule, but rather in the conformation assumed by the complexed state of natural antamanide. The present structure crystallizes in space group P2₁2₁2₁ with a = 20.515(14) Å, b = 21.316(16) Å, c = 17.128(16) Å and four peptide molecules in the unit cell. There are three cocrystallized water molecules at full occupancy intrinsic to the peptide, and several more water molecules or other solvent molecules at partial occupancy. The formula of the peptide is C₆₆ H₁₀₆ N₁₀O₁₀· 4-H₂O·2X.