Mavromoustakos T, Theodoropoulou E, Yang D P, Lin S Y, Koufaki M, Makriyannis A
National Hellenic Research Foundation, Institute of Organic and Pharmaceutical Chemistry, Athens, Greece.
Chem Phys Lipids. 1996 Nov 1;84(1):21-34. doi: 10.1016/s0009-3084(96)02615-1.
Thio analogs of platelet activating factor (PAF) are of great interest because they exhibit antineoplastic properties both in vitro and in vivo. In contrast to most known anticancer agents, these lipids appear not to act through the synthesis and function of DNA and, therefore, offer a new avenue of approaching cancer chemotherapy. We have examined the conformational properties of 1-thiohexadecyl-2-O-methyl-S-glycero-3-phosphocholine (ET-S-16-OCH3) in organic solvents and in micelles. The conformational analysis was based on a combination of 1D, 2D NMR spectroscopy and molecular graphics. 1H and 13C spin lattice relaxation time (T1) experiments were also performed to study the dynamic properties of this molecule. The picture emerging from these studies is as follows. The alkyl chain of ET-S-16-OCH3 is the most mobile part of the molecule both in CDCl3/CD3OD and in micelles and exists as a mixture of interconverting conformers including an extended all trans and several low energy conformers with one or more gauche segments. This creates a twisting of the chain and facilitates a spatial communication between the alkyl chain and the glycerol backbone as well as between the alkyl chain and the headgroup. The methylene groups of the thioglycerol backbone and the headgroup are the least mobile while the methine group of the thioglycerol backbone appears to have an intermediate mobility. The conformation of the thioether lipid in the two media may be of relevance during its interaction with its site of action, the cellular membrane. Such a conformation may also play an important role in determining the selectivity of this interaction with different cell membranes.
血小板活化因子（PAF）的硫代类似物备受关注，因为它们在体外和体内均表现出抗肿瘤特性。与大多数已知的抗癌药物不同，这些脂质似乎并非通过DNA的合成和功能起作用，因此为癌症化疗提供了一条新途径。我们研究了1-硫代十六烷基-2-O-甲基-S-甘油-3-磷酸胆碱（ET-S-16-OCH3）在有机溶剂和胶束中的构象性质。构象分析基于一维、二维核磁共振光谱和分子图形学的结合。还进行了1H和13C自旋晶格弛豫时间（T1）实验，以研究该分子的动态性质。这些研究得出的情况如下。在CDCl3/CD3OD和胶束中，ET-S-16-OCH3的烷基链是分子中最具流动性的部分，以相互转化的构象异构体混合物形式存在，包括伸展的全反式构象和几个具有一个或多个gauche片段的低能量构象。这导致链发生扭曲，并促进了烷基链与甘油主链之间以及烷基链与头部基团之间的空间通信。硫代甘油主链和头部基团的亚甲基流动性最低，而硫代甘油主链的次甲基似乎具有中等流动性。硫醚脂质在这两种介质中的构象在其与作用位点（细胞膜）相互作用过程中可能具有相关性。这种构象在决定与不同细胞膜相互作用的选择性方面也可能起重要作用。
