| 1. |
- Drescher, Simon, et al.
(författare)
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General Synthesis and Aggregation Behaviour of a Series of Single-Chain 1,ω-Bis(phosphocholines)
- 2007
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Ingår i: Chemistry - A European Journal. - : Wiley. - 0947-6539 .- 1521-3765. ; 13:18, s. 5300-5307
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Tidskriftsartikel (refereegranskat)abstract
- The synthesis and physicochem. characterization of a series of polymethylene-1,w-bis(phosphocholines) with even-numbered chain lengths between 22 and 32 carbon atoms is described. Two new synthetic strategies for the prepn. of long-chain 1,wo-diols as hydrocarbon building blocks are presented. The temp.-dependent self-assembly of the single-chain bolaamphiphiles was investigated by cryo transmission electron microscopy (cryo-TEM), differential scanning calorimetry (DSC), and Fourier transform IR spectroscopy (FTIR).
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| 2. |
- Krais, Annette, et al.
(författare)
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Sensitive detection of hydroxymethylcytosine levels in normal and neoplastic cells and tissues.
- 2019
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Ingår i: Electrophoresis. - : Wiley. - 0173-0835 .- 1522-2683. ; 40:9, s. 1293-1297
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Tidskriftsartikel (refereegranskat)abstract
- A new sensitive analytical method using capillary electrophoresis with laser induced fluorescence (CE-LIF) was applied for the simultaneous detection of DNA methylation and hydroxymethylation levels in human cancers of different origin. DNA hydroxymethylation, measured as 5-hydroxymethylcytosine (5hmC) levels, was decreased in gliomas with mutation in the isocitrate dehydrogenase 1 (IDH1) gene when compared to IDH1-wildtype gliomas. Independent from IDH1 mutation, 5hmC levels were decreased in lung carcinomas when compared to normal lung tissue. Reduced DNA hydroxymethylation was also observed upon dedifferentiation in cultured murine embryonic fibroblasts. Our data show that reduced DNA hydroxymethylation is related to cellular dedifferentiation and can be detected in various types of cancers, independent from the IDH1 mutation status. Quantitative determination of altered 5hmC levels may therefore have potential as a biomarker linked to cellular differentiation and tumorigenesis.
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| 3. |
- Meister, Annette, et al.
(författare)
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Temperature-dependent self-assembly and mixing behavior of symmetrical single-chain bolaamphiphiles
- 2008
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Ingår i: Langmuir. - : American Chemical Society (ACS). - 0743-7463 .- 1520-5827. ; 24:12, s. 6238-46
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Tidskriftsartikel (refereegranskat)abstract
- The temp.-dependent self-assembly and the mixing behavior of sym. single-chain bolaamphiphiles with different polymethylene chain lengths and different headgroup structures were investigated in water by differential scanning calorimetry (DSC), cryo transmission electron microscopy (cryo-TEM), and small angle neutron scattering (SANS). The even-numbered polymethylene-1,w-bis(phosphocholines) (PC-Cn-PC) are known to form nanofibers composed of stretched mols. with an all-trans alkyl chain conformation (Drescher, S.; Meister, A.; Blume, A.; Karlsson, G.; Almgren, M.; Dobner, B. Chem.-Eur. J.2007, 13, 5300-5307). The odd-numbered analogs were synthesized to study a possible even-odd effect of these bolaamphiphiles during their aggregation in water. In addn. to these bolaamphiphiles with phosphocholine headgroups, a new series of polymethylene-1,w-bis(phosphodimethylethanolamines) (Me2PE-Cn-Me2PE) with smaller headgroup sizes was synthesized. These bolaamphiphiles show an addnl. fiber-fiber transition when the alkyl chain length exceeds 26 carbon atoms. The mixing behavior of both types of bolaamphiphiles indicates that differences in the alkyl chain length up to six carbon atoms are tolerated within the fiber structure. The mixing of two Me2PE-Cn-Me2PE or PC-Cn-PC type bolaamphiphiles with different alkyl chain lengths offers the possibility to adjust the temp., where the crosslinking of the fibers is disrupted and where the fibers break apart. As a consequence, temp. switchable hydrogels are obtained that can be fine-tuned for drug delivery applications. The comparison with dotriacontane-1,32-diyl-bis[2-(methylammonio)-ethylphosphate] (MePE-C32-MePE), a new bolaamphiphile with even smaller phosphomonomethylammonio headgroups, illustrates the importance of the headgroup size for the aggregation behavior. This bolaamphiphile self-assembles exclusively into lamellar structures, and this aggregate type persists in mixts. with the fiber forming Me2PE-C32-Me2PE.
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| 4. |
- Reuter, Marcel, et al.
(författare)
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Poly-L-lysines and poly-L-arginines induce leakage of negatively charged phospholipid vesicles and translocate through the lipid bilayer upon electrostatic binding to the membrane
- 2009
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Ingår i: Biophysical Chemistry. - : Elsevier BV. - 0301-4622 .- 1873-4200. ; 144:1-2, s. 27-37
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Tidskriftsartikel (refereegranskat)abstract
- Poly-lysines (PLL) and poly-arginines (PLA) of different polymer chain lengths interact strongly with neg. charged phospholipid vesicles mainly due to their different elec. charges. 1-Palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol (POPG), 1,2-dipalmitoyl-sn-glycero-3-phosphoglycerol (DPPG) and their mixts. (1/1 mol/mol) with the resp. phosphatidylcholines of equiv. chain length were chosen as model membrane systems that form at room temp. either the fluid Lalpha or the gel phase Lbeta lipid bilayer membranes, resp. Leakage expts. revealed that the fluid POPG membranes are more perturbed compared to the gel phase DPPG membranes upon peptide binding. Furthermore, it was found that pure PG membranes are more prone to release the vesicle contents as a result of pore formation than the lipid mixts. POPG/POPC and DPPG/DPPC. For the longer polymers (>= 44 amino acids) maximal dye-release was obsd. when the molar ratio of the concns. of amino acid residues to charged lipid mols. reached a value of R P = 0.5, i.e. when the outer membrane layer was theor. entirely covered by the polymer. At ratios lower or higher than 0.5 leakage dropped significantly. Furthermore, PLL and PLA insertions and/or translocations through lipid membranes were analyzed by using FITC-labeled polymers by monitoring their fluorescence intensity upon membrane binding. Short PLL mols. and PLA mols. of all lengths seemed to translocate through both fluid and gel phase lipid bilayers. Comparison of the PLL and PLA fluorescence assay results showed that PLA interacts stronger with phospholipid membranes compared to PLL. Isothermal titrn. calorimetry (ITC) measurements were performed to give further insight into these mechanisms and to support the findings obtained by fluorescence assays. Cryo-transmission electron microscopy (cryo-TEM) was used to visualize changes in the vesicles' morphol. after addn. of the polypeptides.
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| 5. |
- Scholtysek, Peggy, et al.
(författare)
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A T-Shaped Amphiphilic Molecule Forms Closed Vesicles in Water and Bicelles in Mixtures with a Membrane Lipid
- 2012
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Ingår i: Journal of Physical Chemistry B. - : American Chemical Society (ACS). - 1520-6106 .- 1520-5207. ; 116:16, s. 4871-4878
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Tidskriftsartikel (refereegranskat)abstract
- The T-shaped amphiphilic molecule A6/6 forms a columnar hexagonal liquid-crystalline phase between the crystalline and the isotropic liquid when studied in bulk (Chen et al., 2005). Because of the hydrophilic and flexible oligo(oxyethylene) side chain terminated by a 1-acylamino-1-deoxy-d-sorbitol moiety attached to a rigid terphenyl core with terminal hexyloxy alkyl chains, it was expected that also formation of lyotropic phases could be possible. We therefore studied the behavior of A6/6 in water and also in mixtures with bilayer-forming phospholipids, such as dipalmitoyl-phosphatidylcholine (DPPC), using differential scanning calorimetry (DSC), transmission electron microscopy (TEM), cryo-transmission electron microscopy (cryo-TEM), dynamic light scattering (DLS), and solid-state nuclear magnetic resonance (ssNMR). DSC showed for the pure A6/6 suspended in water a phase transition at ca. 23 °C. TEM and cryo-TEM showed vesicular as well as layered structures for pure A6/6 in water below and above this phase transition. By atomic force microscopy (AFM), the thickness of the layer was found to be 5?6 nm. This leads to a model for a bilayer formed by A6/6 with the laterally attached polar side chains shielding the hydrophobic layer built up by the terphenyl core with the terminal alkyl chains of the molecules. For DPPC:A6/6 mixtures (10:1), the DSC curves indicated a stabilization of the lamellar gel phase of DPPC. Negative staining TEM and cryo-TEM images showed planar bilayers with hexagonal morphology and diameters between 50 and 200 nm. The hydrodynamic radius of these aggregates in water, investigated by dynamic light scattering (DLS) as a function of time and temperature, did not change indicating a very stable aggregate structure. The findings lead to the proposition of a new bicellar structure formed by A6/6 with DPPC. In this model, the bilayer edges are covered by the T-shaped amphiphilic molecules preventing very effectively the aggregation to larger structures.
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