Zhou Cun Yu, Wu Haoxing, Devaraj Neal Krishna
Department of Chemistry and Biochemistry , University of California , San Diego , La Jolla , California 92093 , USA . Email:
Chem Sci. 2015 Jul 1;6(7):4365-4372. doi: 10.1039/c5sc00653h. Epub 2015 May 19.
Phospholipids and glycolipids constitute an essential part of biological membranes, and are of tremendous fundamental and practical interest. Unfortunately, the preparation of functional phospholipids, or synthetic analogs, is often synthetically challenging. Here we utilize thiol-yne click chemistry methodology to gain access to phospho- and glycolipid analogs. Alkynyl hydrophilic head groups readily photoreact with numerous thiol modified lipid tails to yield the appropriate dithioether phospho- or glycolipids. The resulting structures closely resemble the structure and function of native diacylglycerolipids. Dithioether phosphatidylcholines (PCs) are suitable for forming giant unilamellar vesicles (GUV), which can be used as vessels for cell-free expression systems. The unnatural thioether linkages render the lipids resistant to phospholipase A2 hydrolysis. We utilize the improved stability of these lipids to control the shrinkage of GUVs composed of a mixture of 1,2-dioleoyl--glycero-3-phosphocholine (DOPC) and dioleyl-dithioether PC, concentrating encapsulated nanoparticles. We imagine that these readily accessible lipids could find a number of applications as natural lipid substitutes.
磷脂和糖脂构成生物膜的重要组成部分，具有巨大的基础研究价值和实际应用价值。遗憾的是，功能性磷脂或其合成类似物的制备往往在合成上具有挑战性。在此，我们利用硫醇-炔点击化学方法来合成磷脂和糖脂类似物。炔基亲水头部基团能与众多硫醇修饰的脂质尾部发生光化学反应，生成相应的二硫醚磷脂或糖脂。所得结构与天然二酰基甘油脂质的结构和功能极为相似。二硫醚磷脂酰胆碱（PCs）适用于形成巨型单层囊泡（GUV），可作为无细胞表达系统的载体。非天然的硫醚键使这些脂质对磷脂酶A2水解具有抗性。我们利用这些脂质提高的稳定性来控制由1,2 - 二油酰基 - 甘油 - 3 - 磷酸胆碱（DOPC）和二油基二硫醚PC混合物组成的GUV的收缩，从而浓缩包裹的纳米颗粒。我们设想这些易于合成的脂质可作为天然脂质替代品有多种应用。
