Synthesis of Nucleosides with 2′‐Fixed Lipid Anchors and Their Behavior in Phospholipid Membranes

Abstract

Various new nucleosides bearing one or two lipophilic groups at the 2′‐position have been synthesized. The lipophilic substituents were attached to a 2′‐hydroxy, 2′‐amino, or 2′‐thio function. These lipophilic nucleosides anchor in large unilamellar POPC vesicles serving as phospholipid membrane models. The insertion of these molecules into the membranes was investigated by NMR techniques. For comparison, nucleosides with two or three lipophilic groups at the 2′‐, 3′‐, or 5′‐positions have also been studied.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)

Interaction of oligonucleotide-based amphiphilic block copolymers with cell membrane models

“…A Langmuir film is formed by spreading insoluble, amphiphilic molecules at a liquid-air interface, and may mimic half a cell membrane [2], with easy control of such properties as composition, lateral pressure, compressibility and molecular density. Of relevance for the DNA-membrane interactions investigated with Langmuir films [3,4] are the increased effects for nucleotides that had their solubility in water reduced, either by alkylation [5] or by linking to a polymer [6]. With increased amphiphilic properties, stronger adsorption of the compound to the air-water interface may occur, while preserving the geometry and integrity of DNA molecules.…”

“…In this case, investigation has been carried out with liposomes [10], micelles [11] and Langmuir monolayers of phospholipids [12,13]. For example, it has been shown that lipophilic nucleosides inserted into liposomes does not disturb considerably the lipid bilayer structure [14][15][16] and also that the nitrogen base interacts with the complementary bases of single-stranded DNA present in the aqueous phase [16,17].…”

2′‐Linking of Lipids and Other Functions to Uridine through 1,2,3‐Triazoles and Membrane Anchoring of the Amphiphilic Products

“…with fatty acids, by carbamate formation, by alkylation, by disulfide formation of 2Ј-thiohydroxy-2Ј-deoxyuridine, or by acylation at 2Ј-amino-2Ј-deoxyuridine. [21][22][23][24][25] The latter was obtained from 2Ј-azido-2Ј-deoxyuridine by Staudinger reduction. [22] Position 2Ј of the nucleosides and oligonucleotides has also been used for tethering other functions such as nucleosides, spin labels, fluorescent labels, electrochemical probes, or terminally functionalized spacer groups.…”

DNA-controlled aggregation of virus like particles – mimicking a tetherin-like mechanism

“…The tocopherol anchors were attached to the nucleobase 29,32,33 rather than to the terminal phosphate moiety. 31,34 The structure of the anchor is shown in the ESI.…”