Dive G, Godfroid J J, Lamotte-Brasseur J, Batt J P, Heymans F, Dupont L, Braquet P
Laboratoire de Microbiologie, Institut de Chimie, Liège, Belgium.
J Lipid Mediat. 1989 Jul-Aug;1(4):201-15.
Three-dimensional electrostatic maps were calculated for six potent antagonists of platelet-activating factor (PAF), the antagonists being selected for their apparent structural heterogeneity. The molecules examined were the compact Ginkgolides BN 52020, BN 52021 and BN 52022 (1, 2 and 3), the semi-rigid kadsurenone (4), a flexible synthetic dinor type C furanoid lignan L-652,731 (5a) and the triazolothienobenzodiazepine WEB 2086 (7). Calculation of the electrostatic potential generated around all the above molecules showed the existence of two wells of negative potential or 'cache-oreilles' (ear-muffs), i.e., the isocontours drawn at -10 kcal/mol, located at 180 degrees from each other and separated by a maximum distance of 22-27 A. Except for the synthetic dinor type C furanoid lignan (5a), the molecules also presented a moderate hydrophobic fragment, which constitutes a third point of interaction with the high-affinity binding site in rabbit and human platelets. The findings of the present study allow speculation that this high-affinity acceptor site may be a 'polarized cylinder' with a diameter of 10-12 A.
针对六种有效的血小板激活因子（PAF）拮抗剂计算了三维静电图，这些拮抗剂因其明显的结构异质性而被挑选出来。所研究的分子包括紧凑的银杏内酯BN 52020、BN 52021和BN 52022（1、2和3）、半刚性的海风藤酮（4）、一种柔性的合成二降C型呋喃类木脂素L-652,731（5a）以及三唑并噻吩并苯二氮䓬WEB 2086（7）。对上述所有分子周围产生的静电势的计算表明，存在两个负电势阱或“耳罩”，即绘制在-10千卡/摩尔处的等势线，它们彼此相隔180度，最大距离为22 - 27埃。除了合成的二降C型呋喃类木脂素（5a）外，这些分子还呈现出一个适度的疏水片段，这构成了与兔和人血小板中高亲和力结合位点相互作用的第三个点。本研究的结果推测，这个高亲和力受体位点可能是一个直径为10 - 12埃的“极化圆柱体”。
