Studies on Functional Role of Archaeal Etherial Lipids

极端嗜盐菌、极端嗜热菌和嗜热嗜酸菌等产甲烷菌在极端条件下生长，具有独特的膜脂结构以适应极端环境。脂质由疏水性类异戊二烯链与甘油醚键连接组成，这与真细菌和真核生物膜脂质的酯键形成鲜明对比。古细菌醚脂质最显著的特征是大环（36或72元）环结构。这些不寻常的脂质已经与基于脂质双层结构的物理化学性质有关。我们对这些脂质的兴趣集中在大环分子结构的生物化学意义上。由于很难从天然来源中获得大量的古菌脂质，因此发展大环脂质的合成方法是先决条件。 ...更多信息 36-和使用McMurry偶联的72元大环脂质。此外，最近还提出了一种利用烯烃复分解制备大环脂质的新方法。在Grubbs的钌-烷叉络合物RuCl_2（=CHPh）（PCy_3）_2存在下，α，ω-二烯在高稀释条件下进行闭环复分解反应，得到36元脂质，产率为79%。通过改变反应条件，无环二烯复分解（ADM）产物主要由相同的底物形成。无环产物随后在高稀释条件下进行RCM反应，得到46%的72元脂质。因此，36元和72元脂质体可以从同一起始原料，通过改变的顺序和条件，在任意获得。36元大环磷脂的物理化学特性进行了研究，并与相应的非环状对应物的脂质体的流动性，热稳定性和渗透性的比较。热分析和单分子膜研究表明，由于36元大环磷脂在烷基链上的运动自由度较低，因此它可以聚集成比相应的无环磷脂更紧密的结构，并且大环结构有助于热稳定膜的形成。这些趋势似乎与嗜热古菌詹氏甲烷球菌对高温的耐受性有关。少

Archaea including methanogens, extreme halophiles, extreme thermophiles and thermoacidophiles grow under rather extraordinary conditions and have structurally unique membrane lipids to adapt the extreme environments. The lipids are consisted of hydrophobic isoprenoid chains linked to glycerol with the ether bonds, which are well contrast to the ester linkage of the eubacterial and eukaryotic membrane lipids. The most striking feature of the archaeal ether lipid is found in the macrocyclic (36- or 72-membered) ring structures. These unusual lipids have been interested in connection with the physicochemical properties based on the lipid bilayer structure. Our interest in these lipids focuses on the biochemical significance of the macrocyclic molecular structures. Prerequisite is to develop synthetic methods of the macrocyclic lipids, because it is difficult to obtain significant amount of the archaeal lipids in pure form from natural sources.We were the first in synthesizing the archaeal … More 36- and 72-membered macrocyclic lipids using McMurry coupling. In addition, a new and efficient approach to the macrocyclic lipids using olefin metathesis has been accomplished recently. In the presence of a Grubbs' ruthenium-alkylidene complex, RuCl_2(=CHPh)(PCy_3)_2, a ring closing metathesis (RCM) of α, ω-diene efficiently proceeded in 79% yield under high dilution conditions to give 36-membered lipid. By changing the reaction conditions, an acyclic diene metathesis (ADM) product was predominantly formed from the same substrate. The acyclic product was subsequently subjected to the RCM reaction under high dilution conditions to provide 72-membered lipid in 46%. Thus, both 36- and 72- membered lipids can be obtained at will from the same starting material only by changing the order and conditions of the metathesis reaction.The physicochemical features of the 36-membered macrocyclic phospholipid were investigated in comparison with the corresponding acyclic counterpart in terms of fluidity, thermostability and permeability of the liposomes. Thermal analyses and monolayer studies indicated that the 36-membered macrocyclic phospholipid can aggregate to more tightly packed structures than the corresponding acyclic counterpart due to its less motional freedom at the alkyl chain region.Furthermore, we found that the macrocyclic structure contributed to the formation of thermally stable membrane. These tendencies appear to be related to the tolerance of thermophilic archaea Methanococcus jannaschii against high temperature. Less