Synthesis and characterization of artificial amide-bearing phospholipids

Synthesis of artificial phospholipids and investigation of the release behavior patterns is the main and novel point of this dissertation. The concept of the amide-bearing artificial phospholipids is based on the replacement of the natural glycerol backbone found in glycerophosphocholines with new interfaces, such as diaminopropanol. A careful study has revealed that the artificial 1,3-disubstituted amide-bearing phospholipids can bear favorable features that differ drastically from the natural phospholipids in the release behavior of their LUVs. The performed experiments included studies of the spontaneous release of 1,2- and 1,3-disubstituted artificial amide-bearing phospholipids at ambient temperature which describes the intrinsic stability of the sample and the release under increased shearing. The study of the thermodynamic properties, morphology and mechanical properties of phospholipid vesicles was performed. The phase transition behavior of artificial amide-bearing phospholipid bilayers and monolayers and the data obtained from TEM, cryo-TEM, BAM and fluorescent microscopy of GUV were analyzed

The synthesis of 1,3-diamidophospholipids

A straightforward synthesis of a small library of 1,3-diamidophospholipids is presented using readily available, cheap reagents and introducing a simple phosphoramidate protecting group strategy

The synthesis of an amine-bearing polymerizable phospholipid

Exchange of the natural glycerol phospholipid backbone with an artificial 1,3-diaminopropanol backbone led to the first synthetic 1,3-diaminophospholipid. The amines in the polar head group region were reacted to acrylamides giving a UV polymerizable phospholipid. Preliminary experiments demonstrate that formulated vesicles can be polymerized into large aggregates of vesicles

Putting the 'P' into Phospholipids

Despite almost hundred years of dedicated research, the synthesis of phospholipids remains a challenge. Here, we briefly review important trends and point out possible future directions that might lead to interesting new probes for the membrane environment. An improved liposome purification and concentration protocol rounds up the article

Solid-State NMR/Dynamic Nuclear Polarization of Polypeptides in Planar Supported Lipid Bilayers

International audienceDynamic nuclear polarization has been developedto overcome the limitations of the inherently low signalintensity of NMR spectroscopy. This technique promises to beparticularly useful for solid-state NMR spectroscopy where thesignals are broadened over a larger frequency range and mostinvestigations rely on recording low gamma nuclei. To extendthe range of possible investigations, a triple-resonance flat-coilsolid-state NMR probe is presented with microwave irradiationcapacities allowing the investigation of static samples attemperatures of 100 K, including supported lipid bilayers. Theprobe performance allows for two-dimensional separated localfield experiments with high-power Lee−Goldberg decoupling and cross-polarization under simultaneous irradiation from agyrotron microwave generator. Efficient cooling of the sample turned out to be essential for best enhancements and line shapeand necessitated the development of a dedicated cooling chamber. Furthermore, a new membrane-anchored biradical ispresented, and the geometry of supported membranes was optimized not only for good membrane alignment, handling, stability,and filling factor of the coil but also for heat and microwave dissipation. Enhancement factors of 17-fold were obtained, and atwo-dimensional PISEMA spectrum of a transmembrane helical peptide was obtained in less than 2 h

Shear-stress sensitive lenticular vesicles for targeted drug delivery

Atherosclerosis results in the narrowing of arterial blood vessels and this causes significant changes in the endogenous shear stress between healthy and constricted arteries. Nanocontainers that can release drugs locally with such rheological changes can be very useful. Here, we show that vesicles made from an artificial 1,3-diaminophospholipid are stable under static conditions but release their contents at elevated shear stress. These vesicles have a lenticular morphology, which potentially leads to instabilities along their equator. Using a model cardiovascular system based on polymer tubes and an external pump to represent shear stress in healthy and constricted vessels of the heart, we show that drugs preferentially release from the vesicles in constricted vessels that have high shear stress