Synthesis of Perdeuterated 1‐Palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine ([D₈₂]POPC) and Characterisation of Its Lipid Bilayer Membrane Structure by Neutron Reflectometry

Abstract

1‐Palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine (POPC), an unsaturated acyl chain containing lipid, is often the predominant lipid in eukaryotic cell membranes in which it is crucial for the fluidity of membranes under physiological conditions. Commercially available, partially deuterated [D31]1‐palmitoyl‐2‐oleoyl‐sn‐glycero‐3‐phosphocholine ([D31]POPC) does not provide sufficient isotopic contrast for detailed structural studies of multicomponent membranes through neutron techniques. Herein, a relatively straightforward and generic chemical deuteration method is discussed for the asymmetric synthesis of perdeuterated [D31]1‐palmitoyl‐[D33]2‐oleoyl‐sn‐[D5]glycero‐[D13]3‐phosphocholine ([D82]POPC) that also allows selective deuteration of any of its constituent groups. Neutron reflectivity of a [D82]POPC‐supported bilayer was used to experimentally determine the neutron scattering length density profile of the lipid. The acyl chains of [D82]POPC are closely contrast‐matched to heavy water, whereas the very high scattering length density of the deuterated glycerophosphocholine head groups provides good contrast to membrane‐binding agents in both deuterated and non‐deuterated solvent environments.

ApoE and ApoE Nascent-Like HDL Particles at Model Cellular Membranes: Effect of Protein Isoform and Membrane Composition

“…1,2-dimyristoyl-sn-glycero-3-phosphocholine (>99%, hDMPC), 1,2-dimyristoyl-d54-sn-glycero-3-phosphocholine (>99%, dDMPC) and cholesterol (h-cholesterol; >98%) were from Avanti Polar Lipids (Alabaster, AL). Tail deuterated 1-palmitoyl, 2-oleoyl-sn-glycero-3-phosphocholine (d67; overall tail deuteration 95%, dPOPC) was provided by the deuteration facility at ANSTO, produced and purified as previously described (Yepuri et al, 2016 ).…”

Towards biomimics of cell membranes: Structural effect of phosphatidylinositol triphosphate (PIP3) on a lipid bilayer

“…Figure 4 shows the NR data collected for the DOPIP3-containing bilayers where, respectively, hPOPC and dPOPC were used. Indeed, it has been extensively demonstrated that selective deuteration of lipids is a very suitable method to vary the contrast between different sample components without affecting their structure [43][44][45][46][47][48][49][50]. In this case the first goal of the data analysis was to investigate the location of PIP3 within the lipid bilayer, i.e.…”

The intriguing journey of gH625-dendrimers

“…This may be due to partialdeuteration effects, preparation conditions for this specic sample, or combinations of both effects. A more perfect bilayer structure can be achieved using fully deuterated POPC, 49 but these molecules are not commercially available yet. We therefore proceeded to study the interaction of this partially deuterated POPC bilayer with our peptide-dendrimer construct.…”