Karle I L
Proc Natl Acad Sci U S A. 1985 Nov;82(21):7155-9. doi: 10.1073/pnas.82.21.7155.
The synthetic analog of antamanide in which all four phenylalanyl residues are hydrogenated to cyclohexylalanyl (Cha) residues, cyclic(Val-Pro-Pro-Ala-Cha-Cha-Pro-Pro-Cha-Cha), has a complete loss of antitoxic potency despite its ability to form ion complexes in the same manner as antamanide. The conformation of Li+.perhydroantamanide has been established in the present paper by x-ray diffraction analysis of a single crystal. The backbone encapsulates a Li+ ion in an almost identical manner as in Li+ antamanide. However, in Li+ antamanide the four phenyl groups are folded against the globular backbone, thus providing a hydrophobic surface for the complex, whereas in Li+ X perhydroantamanide the four cyclohexyl moieties are extended away from the folded backbone, resulting in the exposure of large portions of the polar backbone to the environment. As a consequence, four NH groups form hydrogen bonds with Br- ions, three C--O groups form hydrogen bonds with water molecules, and one C--O group makes a ligand to an additional external Li+ ion. The internal Li+ ion is pentacoordinated, whereas the external Li+ ion is tetracoordinated. The large change of the hydrophobicity around the midsection of the perhydroantamanide complex may be related to the biological inactivity. The content per asymmetric unit of the crystal is C64H102N10O10 X 2Li+ X 4H2O X 2CH3CN.2Br- in space group P2(1)2(1)2(1) with a = 21.740(7), b = 21.566(4), and c = 17.361(4) A. The agreement factor is 8.2% for 5135 data.
将氨甲环酸中所有四个苯丙氨酰残基都氢化为环己氨酰（Cha）残基得到的合成类似物，环（缬氨酸-脯氨酸-脯氨酸-丙氨酸-Cha-Cha-脯氨酸-脯氨酸-Cha-Cha），尽管它能够以与氨甲环酸相同的方式形成离子复合物，但其抗毒效力却完全丧失。本文通过对单晶进行X射线衍射分析确定了Li⁺·全氢氨甲环酸的构象。其主链以与Li⁺·氨甲环酸几乎相同的方式包裹着一个Li⁺离子。然而，在Li⁺·氨甲环酸中，四个苯基靠在球状主链上，从而为复合物提供了一个疏水表面，而在Li⁺·X全氢氨甲环酸中，四个环己基部分从折叠的主链向外伸展，导致大部分极性主链暴露于环境中。结果，四个NH基团与Br⁻离子形成氢键，三个C—O基团与水分子形成氢键，一个C—O基团作为配体与另一个外部Li⁺离子结合。内部的Li⁺离子是五配位的，而外部的Li⁺离子是四配位的。全氢氨甲环酸复合物中部周围疏水性的巨大变化可能与生物活性丧失有关。该晶体每个不对称单元的含量为C₆₄H₁₀₂N₁₀O₁₀·2Li⁺·4H₂O·2CH₃CN·2Br⁻，空间群为P2(1)2(1)2(1)，a = 21.740(7)，b = 21.566(4)，c = 17.361(4) Å。对于5135个数据，拟合因子为8.2%。
