Brasseur R, Serhan C N, Deleers M
Macromolecules at Interfaces, Brussels Free University, Belgium.
Adv Exp Med Biol. 1988;229:93-106. doi: 10.1007/978-1-4757-0937-7_8.
The possible molecular conformations of four structurally and biologically different lipoxins derivatives were predicted by a systematic structure tree theoretical analysis. This method takes into account the London-Van der Waals energy of interaction, the electrostatic interaction, the rotation energy of the torsional angles and the energy of transfer through a possible lipid-water interface. Finally, the conformers derived from the structure tree and with a high probability of existence were submitted to the energy minimization procedure. The most probable conformers of lipoxin A: 5S,6R,15S-trihydroxy-7,9,13 trans-11 cis-eicosatetraenoic acid (LXA); 11 trans lipoxin A: 5S,6R,15S-trihydroxy-7,9,11,13 trans-eicosatetraenoic acid (11t-LXA); lipoxin B: 5S,14R 15S-trihydroxy-6,10,12 trans-8 cis-eicosatetraenoic acid (LXB) and 8 trans lipoxin B: 5S,14R,15S-trihydroxy- 6,8,10,12 trans-eicosatetraenoic acid (8t-LXB) in their isolated form or when forming complexes with one calcium ion are presented. The four isolated compounds lead to vastly different conformations. Lipoxin A can form the most globular conformer while lipoxin B seems to be slightly more extended. The all trans isomer of lipoxin B forms an extended conformer and 11 trans lipoxin A gives a fully extended molecule. Complexes of a pair of these compounds with one calcium ion were shown to lead to vastly different conformations. Both (LXA) 2Ca and (LXB)2Ca form crumpled or extended structure, the LXA molecules being more wrapped around Ca2+ than LXB molecules. The (11t-LXA)2Ca and (8t-LXB)2Ca complexes present a high probability of extended conformations. Our description merely shows that the peculiar stereochemistry of these molecules lead to equilibria between conformers or to very static conformers, the flexibility and rigidity of which being probably relevant in view of their different biological activities.
通过系统的结构树理论分析预测了四种结构和生物学特性不同的脂氧素衍生物可能的分子构象。该方法考虑了伦敦 - 范德华相互作用能、静电相互作用、扭转角的旋转能以及通过可能的脂质 - 水界面的转移能。最后，将从结构树中得出且存在概率高的构象异构体进行能量最小化处理。展示了脂氧素A：5S,6R,15S - 三羟基 - 7,9,13反式 - 11顺式 - 二十碳四烯酸（LXA）；11反式脂氧素A：5S,6R,15S - 三羟基 - 7,9,11,13反式 - 二十碳四烯酸（11t - LXA）；脂氧素B：5S,14R 15S - 三羟基 - 6,10,12反式 - 8顺式 - 二十碳四烯酸（LXB）和8反式脂氧素B：5S,14R,15S - 三羟基 - 6,8,10,12反式 - 二十碳四烯酸（8t - LXB）在其分离形式或与一个钙离子形成复合物时的最可能构象。这四种分离的化合物导致了截然不同的构象。脂氧素A能形成最球状的构象异构体，而脂氧素B似乎稍微更伸展一些。脂氧素B的全反式异构体形成一个伸展的构象异构体，11反式脂氧素A产生一个完全伸展的分子。这些化合物中的一对与一个钙离子形成的复合物显示出导致截然不同的构象。（LXA）2Ca和（LXB）2Ca都形成皱缩或伸展的结构，LXA分子比LXB分子更紧密地围绕Ca2+。（11t - LXA）2Ca和（8t - LXB）2Ca复合物呈现出伸展构象的高概率。我们的描述仅仅表明这些分子独特的立体化学导致构象异构体之间的平衡或非常静态的构象异构体，鉴于它们不同的生物活性，其柔韧性和刚性可能是相关的。
