Convenient synthesis and application of versatile nucleic acid lipid membrane anchors in the assembly and fusion of liposomes

Abstract

Hydrophobic moieties like lipid membrane anchors are highly demanded modifications for nucleic acid oligomers. Membrane-anchor modified oligonucleotides are applicable in biomedicine leading to new delivery strategies as well as in biophysical investigations towards the assembly and fusion of liposomes or the construction of DNA origami structures. We present herein the synthesis and applications of versatile lipid membrane anchor building blocks suitable for solid-supported oligonucleotide synthesis. These are readily synthesized in bulk in five to seven steps from commercially available precursors and can be incorporated at any position within an oligonucleotide without significantly altering the duplex stability and structure as was proven by thermal denaturation experiments and circular dichroism. Furthermore, their applicability could be demonstrated by the assembly and fusion of liposomes mediated by lipid-modified oligonucleotides.