Brea Roberto J, Cole Christian M, Devaraj Neal K
Department of Chemistry and Biochemistry, University of California, San Diego, 9500 Gilman Drive, Urey Hall 4120, La Jolla, CA 92093 (USA) http://devarajgroup.ucsd.edu.
Angew Chem Int Ed Engl. 2014 Dec 15;53(51):14102-5. doi: 10.1002/anie.201408538. Epub 2014 Oct 24.
Phospholipid vesicles are of intense fundamental and practical interest, yet methods for their de novo generation from reactive precursors are limited. A non-enzymatic and chemoselective method to spontaneously generate phospholipid membranes from water-soluble starting materials would be a powerful tool for generating vesicles and studying lipid membranes. Here we describe the use of native chemical ligation (NCL) to rapidly prepare phospholipids spontaneously from thioesters. While NCL is one of the most popular tools for synthesizing proteins and nucleic acids, to our knowledge this is the first example of using NCL to generate phospholipids de novo. The lipids are capable of in situ synthesis and self-assembly into vesicles that can grow to several microns in diameter. The selectivity of the NCL reaction makes in situ membrane formation compatible with biological materials such as proteins. This work expands the application of NCL to the formation of phospholipid membranes.
磷脂囊泡具有重要的基础研究价值和实际应用意义，然而从活性前体从头生成磷脂囊泡的方法却很有限。一种从水溶性起始原料自发生成磷脂膜的非酶促化学选择性方法，将成为生成囊泡和研究脂质膜的有力工具。在此，我们描述了利用天然化学连接（NCL）从硫酯快速自发制备磷脂的方法。虽然NCL是合成蛋白质和核酸最常用的工具之一，但据我们所知，这是首次使用NCL从头生成磷脂的实例。这些脂质能够原位合成并自组装成直径可达数微米的囊泡。NCL反应的选择性使得原位膜形成能够与蛋白质等生物材料兼容。这项工作拓展了NCL在磷脂膜形成方面的应用。
