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Dive into the research topics where Peter Nuhn is active.

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Featured researches published by Peter Nuhn.


Chemistry and Physics of Lipids | 1986

Synthesis, calorimetry, and X-ray diffraction of lecithins containing branched fatty acid chains.

Peter Nuhn; G. Brezesinski; Bodo Dobner; Günter Förster; Michael Gutheil; H. D. Dörfler

Lecithins with branched fatty acid chains were synthesized and characterized by differential scanning calorimetry and X-ray diffraction. The influence of three chemical alterations on the phase transition parameters were investigated: length of the branches in 2-position of the acyl chains, position of the branches in the acyl chains, and position of the branched fatty acid chains in the glycerol backbone. The results show that the branched phosphatidylcholines (PCs) have a reduced gel-to-liquid-crystalline phase transition temperature (Tm) compared to the corresponding straight-chain PCs. Depending on both the length of the branches in 2-position of the acyl chains and the position of the branches in the acyl chains, the Tm-values pass through a minimum. The systematic change of the main-transition temperatures Tm is connected with a modified structural polymorphism. If the length of the branches increases three types of polymorphism were observed.


Pharmaceutical Research | 2003

Influence of Spacer Length on Interaction of Mannosylated Liposomes with Human Phagocytic Cells

Andreas Engel; Swapan Kumar Chatterjee; Ali Hamed Al-Arifi; Dagmar Riemann; Jürgen Langner; Peter Nuhn

AbstractPurpose. To improve target specificity and uptake of liposomes by macrophages, one can improve high-affinity receptor binding to mannose determinants with their 175-kDa mannose receptor (MR), which is mainly influenced by the length and flexibility of the spacer between the carbohydrate head group and liposome surface. Liposomes containing alkylmannosides with hydrophilic spacers 0 to 8 ethyleneoxy units (EO) long (Man0...Man8) were used to investigate systematically the effects of spacer length on liposome-cell interactions. Methods. Concanavalin A (ConA)-induced liposome aggregation was studied by turbidity measurement and cell uptake using PMA-induced HL-60 cells or native human macrophages by determining 6-CF after cell lysis or NBD-fluorescence with flow cytometry. Detection of MR in native cell populations was carried out by an antibody assay using flow cytometry; MR-representing cells were selected analytically. Results. Liposomes containing mannosides with more than one EO spacer length were specifically aggregated by ConA, indicating accessibility of the carbohydrate ligands of these derivatives. Increase in EO spacer units of incorporated mannosides (two or more EO) led to suppression of cellular uptake of mannosylated liposomes by phago- cytes lacking MR (HL60, U937). The extent of suppression increased with spacer length. Liposome uptake by native macrophages expressing MR was, on the contrary, improved, particularly by Man6 and Man8. Conclusions. Uptake of liposomes modified with Man6 or Man8 by native cells was enhanced but did not reach an optimum. Thus, Man6, Man8, and mannosides with even longer spacer arms are of potential use in receptor-mediated targeting.


Journal of Controlled Release | 1994

The protective effect of free and membrane-bound cryoprotectants during freezing and freeze-drying of liposomes

Michael Ausborn; Hans Schreier; G. Brezesinski; Heinz Fabian; Helmut W. Meyer; Peter Nuhn

Liposomes were prepared from natural (EPC) and hydrogenated (HEPC) egg phosphatidylcholine, with and without cholesterol (CHOL), from sucrose fatty acid ester (SPS7; sucrose-palmitate/stearate) with CHOL and dicetylphosphate (DCP) or from EPC and HEPC with the mono-, di- and tri-ester of SPS7. The cryoprotective activity of sucrose or membrane-bound sucrose fatty esters was assessed. Vesicles were frozen and thawed, or freeze-dried and reconstituted, and retention of the encapsulated marker 5,6-carboxyfluorescein (CF) was monitored. CF retentio n decreased with decreasing freezing temperature, while increasing concentrations of sucrose provided increasing cryoprotection during freezing and thawing. SPS7 vesicles were fully protected by 0.6 M sucrose, whereas equimolar mixtures of EPC and HEPC with SPS7 required 1 M sucrose for complete protection. EPC/CHOL liposomes retained maximally 85% and HEPC/CHOL liposomes 95% marker at the highest sucrose concentration. Lyophilized liposomes without sucrose or in mixture with the SPS mono- or diester retained <10% CF. Lyophilization of EPC and HEPC liposomes in the presence of 0.4 M sucrose resulted in 75% retention of originally encapsulated marker. Differential scanning calorimetry showed a significant reduction of the transition temperature (Tc) of lyophilized HEPC liposomes in the presence of sucrose and the SPS monoester. Infrared spectroscopy indicated sucrose and the SPS monoester forming strong hydrogen bonds with phosphate head groups which supports the water replacement of ‘pseudohydration’ hypothesis.


Biochemical Pharmacology | 1992

Phospholipase A2 inhibition by alkylbenzoylacrylic acids

Thomas Köhler; M. Heinisch; Matthias Kirchner; G. Peinhardt; R. Hirschelmann; Peter Nuhn

3-(4-Alkylbenzoyl)acrylic acids (ABAAs) were synthesized by acylation of alkylbenzenes with maleic anhydride and then screened in vitro for inhibition of phospholipase A2 (PLA2) from snake venom and from porcine pancreas. The inhibitory potency of ABAAs increased with the length of the alkyl residues resulting in IC50 values of between 10(-7) and 10(-4) mol/L. The most potent inhibitors of the snake venom PLA2 were the 4-(n)-hexadecyl and octadecyl (OBAA) derivatives. Kinetic experiments referred to a time-dependent inhibitory reaction. Irreversibility was examined by dilution and dialysis. A molar ratio of inactivation of OBAA of nearly 20 was estimated. Double reciprocal replots of the apparent inactivation constants to the concentration of OBAA gave a (pseudo) first order rate constant of inactivation of 2.3 min-1. For the dissociation constant of the enzyme-inhibitor intermediate, a value of 6 x 10(-6) mol/L was obtained. On the other hand, the PLA2 from porcine pancreas seemed hardly to be inhibited by ABAAs. The present data are discussed in relation to the proposed model for PLA2 inactivation by manoalide. In human PMNs leukotriene B4 and 5-HETE production was essentially reduced. In human platelets the thrombin-induced TxA2 production was reduced. Since these effects disappeared after addition of arachidonic acid, these findings refer to a PLA2 inhibition. The immunologically induced bronchospasm in guinea pigs was significantly and dose-dependently inhibited by OBAA. This indicates that ABAAs might be useful in treating allergic diseases, such as asthma, eczema, allergic shock and others.


Archives of Toxicology | 1985

Radioimmunoassay for 2,4-dichlorophenoxyacetic acid

Dietmar Knopp; Peter Nuhn; Hans-Joachim Dobberkau

Antisera to 2,4-dichlorophenoxyacetic acid (2,4-D), a widely used herbicide, have been obtained from rabbits following immunization with various 2,4-D-protein conjugates. Employing [125I] 2,4-D-tyramine as the radioligand for the antisera, very poor assay sensitivity was achieved because of a much higher affinity of the antibodies to the tracer. When using [6-3H] 2,4-D(specific radioactivity 465 GBq/mmol) a sensitive and specific radioimmunoassay (RIA) for 2,4-D could be developed, which allows determination directly in water, plasma and urine samples. Levels as low as approximately 100 pg (450 femtomoles) of 2,4-D can be detected. The antiserum is fairly specific for 2,4-D. Other related phenoxycarboxylic acids and dichlorophenol showed a cross-reactivity smaller than 10%. After a single administration of 2,4-D (0.91 mg/100 g body weight, orally) to rats, plasma and urine levels were determined at different times. Results correspond to those found in the literature, thus indicating the utility of the RIA. Further applications and limitations are discussed.


Chemistry and Physics of Lipids | 1987

Influence of α-branched fatty acid chains on the thermotropic behaviours of 1-O-acyl-2-O-hexadecyl-glycerophosphocholines

G. Brezesinski; Bodo Dobner; H. D. Dörfler; Michael Fischer; Steffi Haas; Peter Nuhn

Abstract Phosphatidylcholines containing a branched-chain fatty acid in 1-position at the glycerol backbone were synthesized and characterized by differential scanning calorimetry; We find that their thermotropic phase behaviour depends on the length of the branches. The results show that, depending on the side-chain length, the gel-to-liquid-crystalline phase transition temperatures ( T m ) pass through a minimum. The systematic change of the T m -values is connected with a modified temperature dependence of the apparent molar heat capacities.


Biophysical Journal | 1996

Chiral discrimination in a monolayer of a triple-chain phosphatidylcholine.

Frank Bringezu; Gerald Brezesinski; Peter Nuhn; H. Möhwald

Monolayers of an enantiomeric and a racemic triple-chain phosphatidylcholine (PC) at the air/water interface are studied by film balance measurements and x-ray diffraction. Although the area per three tails exceeds that per head, we observe tail ordering dependent on headgroup chirality and chain tilt. This indicates lateral headgroup interactions. The influence of the chiral carbon is suppressed at higher lateral pressures, and a centered-rectangular unit cell with tails tilted into the nearest neighbor (NN) direction is observed for both the enantiomer and the racemate. The distortion of the lattice changes at medium pressures from NN to NNN (next-nearest neighbor direction) with decreasing temperature. The phase behavior of the racemate at 15 degrees C is compared with that of a triple-chain PC with a branched chain of reduced length. Whereas the PC with the longer branched chain exhibits only a NN tilted phase at all pressures, the PC with the shorter branched chain has a rich polymorphism (NNN-NN-upright hexagonal packing) under increased lateral pressure.


International Journal of Pharmaceutics | 1994

Freeze drying of liposomes with free and membrane-bound cryoprotectants — the background of protection and damaging processes

A. Engel; Gerd Bendas; F. Wilhelm; M. Mannova; M. Ausborn; Peter Nuhn

Abstract Studies of the protective effects of different amounts of sucrose and glucose and a carbohydrate directly linked to the liposome surface on large unilamellar vesicles (LUV) built from soybean phosphatidylcholine (SPC) during lyophilization were carried out. Analyses of freeze-dried liposomes were conducted by particle size determination, retention of entrapped water-soluble marker and lipid mixing assay employing resonance energy transfer (RET). The extent of functionality of carbohydrates depends on their concentration and results from spacing mainly preventing fusion at low concentrations, membrane stabilization preventing leakage and the bulk sugar matrix mainly depressing aggregation at higher concentrations. By incorporating hexadecyl-β- D -galactopyranoside in SPC-LUV as membrane-bound cryoprotectant it could be shown that fixation of the sugar head of galactosides at the membrane surface only leads to prevention of fusion of liposomes. Although the galactoside does not exhibit a membrane stabilizing effect alone, it improves the protective effects of the free carbohydrates hyperadditively. However, this fact is discussed on the basis of sugar-sugar interactions by means of hydrogen bonding.


Analytica Chimica Acta | 2003

Normal-phase liquid chromatographic separation of stratum corneum ceramides with detection by evaporative light scattering and atmospheric pressure chemical ionization mass spectrometry

Hany Farwanah; Peter Nuhn; Reinhard H.H. Neubert; Klaus Raith

A new normal-phase HPLC method for the separation of stratum corneum ceramides is presented. Separation was achieved in less than 15 min using a binary gradient consisting of chloroform, n-propanol and acetic acid. Since UV and fluorescence detection are not possible without derivatization and electrospray MS is not compatible to normal-phase LC, we have investigated evaporative light scattering detection (ELSD) and atmospheric pressure chemical ionization mass spectrometry (APCI-MS). When comparing both detection methods, it can be stated that APCI-MS was more sensitive and provides more structural information. However, ELSD can be an economic alternative for routine analysis. The method was applied to human stratum corneum ceramides obtained by lipid extraction. It was shown that the peaks found in LC correspond to the bands described for TLC. The conversion of TLC procedures to HPLC enables an online coupling to mass spectrometry, which is particularly useful in the investigation of changed lipid patterns caused by skin diseases such as psoriasis and atopic dermatitis.


Chemistry and Physics of Lipids | 1977

NMR and calorimetric studies of changes in phase transition of head group modified phospholipids

K. Gawrisch; Klaus Arnold; H.-J. Rüger; P. Kertscher; Peter Nuhn

The 13C- and 31P-NMR spectra and DSC thermograms of unsonicated dispersions consisting of phospholipids of varying methylation stages of the propanolamine head group were investigated. Methylation of the head group was accompanied by a corresponding reduction in the phase transition temperatures. In the liquid crystalline state the 31P-anisotropy of the chemical shift is about equal for all studied compounds, demonstrating that the motion of the phosphate group is not influenced by modifications of the propanolamine group.

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