Meng Zhuojun, Yang Jian, Liu Qing, de Vries Jan Willem, Gruszka Agnieszka, Rodríguez-Pulido Alberto, Crielaard Bart J, Kros Alexander, Herrmann Andreas
Zernike Institute for Advanced Materials, University of Groningen, Nijenborgh 4, 9747 AG, Groningen, The Netherlands.
Supramolecular & Biomaterials Chemistry, Leiden Institute of Chemistry, Leiden University, P.O. Box 9502, 2300 RA, Leiden, The Netherlands.
Chemistry. 2017 Jul 12;23(39):9391-9396. doi: 10.1002/chem.201701379. Epub 2017 Jun 20.
Anchoring DNA via hydrophobic units into the membrane of vesicles allows tagging of these nanocontainers with sequence information. Moreover, the hybridization of DNA on the surface of liposomes enables sequence specific functionalization, vesicle aggregation, and vesicle fusion. Specifically, DNA-hybridization-based approaches for fusion employing oligonucleotides terminally modified with one or two anchoring units were hindered by a limited degree of full fusion or by significant leakage during fusion. The current work deals with a new strategy for anchoring oligonucleotides on a membrane by lipid-modified nucleobases rather than by attaching hydrophobic units to the 3'- or 5'-termini. The lipid anchors were incorporated into the DNA sequence via phosphoramidite nucleotide building blocks during automated solid-phase synthesis allowing variation of the number and position of hydrophobic units along the DNA backbone. Single-stranded DNA functionalized with four lipid-modified nucleobases was stably grafted onto the membrane of lipid vesicles. It was found that the orientation of DNA hybridization and the number of anchoring units play a crucial role in liposomal fusion, which in the most efficient system reached remarkable 29 % content mixing without notable leakage.
通过疏水单元将DNA锚定到囊泡膜上，能够用序列信息标记这些纳米容器。此外，脂质体表面的DNA杂交可实现序列特异性功能化、囊泡聚集和囊泡融合。具体而言，采用末端用一个或两个锚定单元修饰的寡核苷酸进行基于DNA杂交的融合方法，受到完全融合程度有限或融合过程中大量泄漏的阻碍。当前的工作涉及一种新策略，即通过脂质修饰的核碱基而非将疏水单元连接到3'或5'末端，将寡核苷酸锚定在膜上。在自动固相合成过程中，通过亚磷酰胺核苷酸构建块将脂质锚掺入DNA序列，从而可以改变疏水单元沿DNA主链的数量和位置。用四个脂质修饰核碱基功能化的单链DNA稳定地接枝到脂质囊泡膜上。研究发现，DNA杂交的方向和锚定单元的数量在脂质体融合中起着关键作用，在最有效的系统中，内容物混合率达到了显著的29%，且无明显泄漏。
